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1.
Nat Immunol ; 25(9): 1546-1554, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39134750

RESUMO

Tumor angiogenesis and immunity show an inverse correlation in cancer progression and outcome1. Here, we report that ZBTB46, a repressive transcription factor and a widely accepted marker for classical dendritic cells (DCs)2,3, controls both tumor angiogenesis and immunity. Zbtb46 was downregulated in both DCs and endothelial cells by tumor-derived factors to facilitate robust tumor growth. Zbtb46 downregulation led to a hallmark pro-tumor microenvironment (TME), including dysfunctional vasculature and immunosuppressive conditions. Analysis of human cancer data revealed a similar association of low ZBTB46 expression with an immunosuppressive TME and a worse prognosis. In contrast, enforced Zbtb46 expression led to TME changes to restrict tumor growth. Mechanistically, Zbtb46-deficient endothelial cells were highly angiogenic, and Zbtb46-deficient bone marrow progenitors upregulated Cebpb and diverted the DC program to immunosuppressive myeloid lineage output, potentially explaining the myeloid lineage skewing phenomenon in cancer4. Conversely, enforced Zbtb46 expression normalized tumor vessels and, by suppressing Cebpb, skewed bone marrow precursors toward immunostimulatory myeloid lineage output, leading to an immune-hot TME. Remarkably, Zbtb46 mRNA treatment synergized with anti-PD1 immunotherapy to improve tumor management in preclinical models. These findings identify ZBTB46 as a critical factor for angiogenesis and for myeloid lineage skewing in cancer and suggest that maintaining its expression could have therapeutic benefits.


Assuntos
Células Dendríticas , Neovascularização Patológica , Microambiente Tumoral , Animais , Microambiente Tumoral/imunologia , Camundongos , Neovascularização Patológica/imunologia , Neovascularização Patológica/genética , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/genética , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/imunologia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Feminino , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Camundongos Knockout , Angiogênese , Fatores de Transcrição
2.
PLoS Biol ; 21(5): e3001746, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37134077

RESUMO

Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, respectively. IL-1α induced TNFα expression in splenic HSPCs, which then activated splenic niche activity, while LIF induced proliferation of splenic niche cells. IL-1α and LIF display cooperative effects in activating EMH and are both up-regulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.


Assuntos
Doenças Hematológicas , Hematopoese Extramedular , Neoplasias , Humanos , Animais , Camundongos , Hematopoese Extramedular/fisiologia , Fator Inibidor de Leucemia/farmacologia , Interleucina-1alfa/farmacologia , Hematopoese
3.
Curr Issues Mol Biol ; 46(6): 5420-5435, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38920996

RESUMO

Melanocytes, located in the epidermis' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and ß-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and ß-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.

4.
Small ; 20(9): e2306468, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37857588

RESUMO

Organic semiconductors have great potential to revolutionize electronics by enabling flexible and eco-friendly manufacturing of electronic devices on plastic film substrates. Recent research and development led to the creation of printed displays, radio-frequency identification tags, smart labels, and sensors based on organic electronics. Over the last 3 decades, significant progress has been made in realizing electronic devices with unprecedented features, such as wearable sensors, disposable electronics, and foldable displays, through the exploitation of desirable characteristics in organic electronics. Neverthless, the down-scalability of organic electronic devices remains a crucial consideration. To address this, efforts are extensively explored. It is of utmost importance to further develop these alternative patterning methods to overcome the downscaling challenge. This review comprehensively discusses the efforts and strategies aimed at overcoming the limitations of downscaling in organic semiconductors, with a particular focus on four main areas: 1) lithography-compatible organic semiconductors, 2) fine patterning of printing methods, 3) organic material deposition on pre-fabricated devices, and 4) vertical-channeled organic electronics. By discussing these areas, the full potential of organic semiconductors can be unlocked, and the field of flexible and sustainable electronics can be advanced.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39340800

RESUMO

OBJECTIVES: Certain studies propose that antibiotic use may influence rheumatoid arthritis (RA) incidence, but the clear association between antibiotics and RA remains unclear. Therefore, this study aimed to examine the relationship between antibiotics and RA risk to provide additional epidemiological evidence. METHODS: This population-based retrospective cohort study was conducted with adults aged 40 years or older using the Korean National Health Insurance Service (NHIS) database. Antibiotic exposure was measured from 2003 to 2007. Study participants were followed up from January 1, 2008, to December 31, 2019. Multivariable Cox hazard regression was utilized to evaluate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of RA according to accumulative days of antibiotic use and the number of antibiotic classes used, respectively. RESULTS: During 3,395 590 person-years of follow-up, 29 274 cases of RA were identified. Participants who used antibiotics for 91 or more days had a higher risk of RA (aHR, 1.79; 95% CI, 1.67-1.92) than antibiotic non-users. Additionally, individuals who used four or more kinds of antibiotic classes had a higher risk of RA (aHR, 1.61; 95% CI, 1.51-1.71) than those who did not prescribe antibiotics. The risk of RA was positively associated with both higher cumulative days of antibiotic exposure and a larger number of drug classes. These trends were maintained in sensitivity analyses, including variations in antibiotic exposure periods. CONCLUSION: Our findings suggest a possible association between the long-term use of antibiotics and RA incidence. Further studies are necessary for a clearer understanding of this association.

6.
J Nanobiotechnology ; 22(1): 347, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898529

RESUMO

BACKGROUND: Silica nanoparticles (SNPs) have immense potential in biomedical research, particularly in drug delivery and imaging applications, owing to their stability and minimal interactions with biological entities such as tissues or cells. RESULTS: With synthesized and characterized cyanine-dye-doped fluorescent SNPs (CSNPs) using cyanine 3.5, 5.5, and 7 (Cy3.5, Cy5.5, and Cy7). Through systematic analysis, we discerned variations in the surface charge and fluorescence properties of the nanoparticles contingent on the encapsulated dye-(3-aminopropyl)triethoxysilane conjugate, while their size and shape remained constant. The fluorescence emission spectra exhibited a redshift correlated with increasing dye concentration, which was attributed to cascade energy transfer and self-quenching effects. Additionally, the fluorescence signal intensity showed a linear relationship with the particle concentration, particularly at lower dye equivalents, indicating a robust performance suitable for imaging applications. In vitro assessments revealed negligible cytotoxicity and efficient cellular uptake of the nanoparticles, enabling long-term tracking and imaging. Validation through in vivo imaging in mice underscored the versatility and efficacy of CSNPs, showing single-switching imaging capabilities and linear signal enhancement within subcutaneous tissue environment. CONCLUSIONS: This study provides valuable insights for designing fluorescence imaging and optimizing nanoparticle-based applications in biomedical research, with potential implications for targeted drug delivery and in vivo imaging of tissue structures and organs.


Assuntos
Carbocianinas , Corantes Fluorescentes , Nanopartículas , Imagem Óptica , Dióxido de Silício , Dióxido de Silício/química , Nanopartículas/química , Carbocianinas/química , Animais , Camundongos , Imagem Óptica/métodos , Corantes Fluorescentes/química , Humanos , Silanos/química , Tamanho da Partícula , Propilaminas , Benzotiazóis
7.
BMC Genomics ; 24(1): 613, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37828501

RESUMO

BACKGROUND: The domestic dog, Canis lupus familiaris, is a companion animal for humans as well as an animal model in cancer research due to similar spontaneous occurrence of cancers as humans. Despite the social and biological importance of dogs, the catalogue of genomic variations and transcripts for dogs is relatively incomplete. RESULTS: We developed CanISO, a new database to hold a large collection of transcriptome profiles and genomic variations for domestic dogs. CanISO provides 87,692 novel transcript isoforms and 60,992 known isoforms from whole transcriptome sequencing of canine tumors (N = 157) and their matched normal tissues (N = 64). CanISO also provides genomic variation information for 210,444 unique germline single nucleotide polymorphisms (SNPs) from the whole exome sequencing of 183 dogs, with a query system that searches gene- and transcript-level information as well as covered SNPs. Transcriptome profiles can be compared with corresponding human transcript isoforms at a tissue level, or between sample groups to identify tumor-specific gene expression and alternative splicing patterns. CONCLUSIONS: CanISO is expected to increase understanding of the dog genome and transcriptome, as well as its functional associations with humans, such as shared/distinct mechanisms of cancer. CanISO is publicly available at https://www.kobic.re.kr/caniso/ .


Assuntos
Neoplasias , Lobos , Cães , Animais , Humanos , Transcriptoma , Lobos/genética , Genoma , Genômica , Neoplasias/genética , Neoplasias/veterinária , Isoformas de Proteínas/genética
8.
Small ; 19(35): e2208144, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37096940

RESUMO

Adhesion lithography offers to fabrication of coplanar asymmetric nanogap electrodes with a low-cost and facile process. In this study, a gate-tunable diode with coplanar asymmetric nanogap is fabricated using adhesion lithography. A fluoropolymer material is introduced to the adhesion lithography process to ensure a manufacturing patterning process yield as high as 96.7%. The asymmetric electrodes formed a built-in potential, leading to rectifying behavior. The coplanar electrode structure allowed the use of a gate electrode in vertical contact with the channel, resulting in gate-tunable diode characteristics. The nanoscale channel induced a high current density (3.38 × 10-7  A∙cm-1 ), providing a high rectification ratio (1.67 × 105  A∙A-1 ). This rectifier diode is confirmed to operate with pulsed input signals and suggests the gate-tunability of nanogap diodes.

9.
Nucleic Acids Res ; 49(D1): D38-D46, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33245777

RESUMO

Three-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due to the lack of appropriate tools specialized for disorganized higher-order chromatin structure. Here, we updated a 3D-genome Interaction Viewer and database named 3DIV by uniformly processing ∼230 billion raw Hi-C reads to expand our contents to the 3D cancer genome. The updates of 3DIV are listed as follows: (i) the collection of 401 samples including 220 cancer cell line/tumor Hi-C data, 153 normal cell line/tissue Hi-C data, and 28 promoter capture Hi-C data, (ii) the live interactive manipulation of the 3D cancer genome to simulate the impact of structural variations and (iii) the reconstruction of Hi-C contact maps by user-defined chromosome order to investigate the 3D genome of the complex genomic rearrangement. In summary, the updated 3DIV will be the most comprehensive resource to explore the gene regulatory effects of both the normal and cancer 3D genome. '3DIV' is freely available at http://3div.kr.


Assuntos
Biologia Computacional , Bases de Dados Genéticas , Genômica , Neoplasias/genética , Biologia Computacional/métodos , Epigenômica/métodos , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Humanos , Software
10.
Nucleic Acids Res ; 49(D1): D956-D961, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33137185

RESUMO

High-throughput screening based on CRISPR-Cas9 libraries has become an attractive and powerful technique to identify target genes for functional studies. However, accessibility of public data is limited due to the lack of user-friendly utilities and up-to-date resources covering experiments from third parties. Here, we describe iCSDB, an integrated database of CRISPR screening experiments using human cell lines. We compiled two major sources of CRISPR-Cas9 screening: the DepMap portal and BioGRID ORCS. DepMap portal itself is an integrated database that includes three large-scale projects of CRISPR screening. We additionally aggregated CRISPR screens from BioGRID ORCS that is a collection of screening results from PubMed articles. Currently, iCSDB contains 1375 genome-wide screens across 976 human cell lines, covering 28 tissues and 70 cancer types. Importantly, the batch effects from different CRISPR libraries were removed and the screening scores were converted into a single metric to estimate the knockout efficiency. Clinical and molecular information were also integrated to help users to select cell lines of interest readily. Furthermore, we have implemented various interactive tools and viewers to facilitate users to choose, examine and compare the screen results both at the gene and guide RNA levels. iCSDB is available at https://www.kobic.re.kr/icsdb/.


Assuntos
Sistemas CRISPR-Cas/genética , Bases de Dados Genéticas , Edição de Genes/métodos , Marcação de Genes/métodos , Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Linhagem Celular Tumoral , Humanos , Internet , Navegador
11.
Br J Nutr ; 124(5): 513-520, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31452484

RESUMO

Body weight is a major risk determinant of frailty, but the effect of obesity on frailty is controversial. The present study aimed to confirm the hypothesis that the risk of frailty is positively associated with obesity (BMI ≥ 30 kg/m2), but the association is mediated by the waist:height ratio (WHtR) in older women and men. A total of 2862 community-dwelling older individuals aged 70-84 years were assessed for frailty using the Korean version of Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight index. Obesity (BMI ≥ 30 kg/m2) was associated with a higher risk of frailty compared with BMI 18·5-<23 kg/m2 in all the older individuals (OR 1·88; 95 % CI 1·11, 3·17; P = 0·018) and in older women (OR 1·86; 95 % CI 1·01, 3·42; P = 0·047) before adjusting for WHtR but was not associated with BMI after adjusting for WHtR. Additionally, obesity was not significantly associated with the risk of frailty before and after adjusting for WHtR in older men. Mediation analysis revealed that the association between BMI and frailty score was mediated by WHtR. Moreover, the mediating effect of WHtR on frailty score was positive in both women and men, but the frailty score was associated with BMI positively in women and negatively in men. The present study suggests that the risk of frailty is higher in obese women, which is mediated by WHtR, but not in obese men.


Assuntos
Envelhecimento/fisiologia , Índice de Massa Corporal , Idoso Fragilizado , Razão Cintura-Estatura , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , República da Coreia
12.
Nucleic Acids Res ; 46(D1): D52-D57, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29106613

RESUMO

Three-dimensional (3D) chromatin structure is an emerging paradigm for understanding gene regulation mechanisms. Hi-C (high-throughput chromatin conformation capture), a method to detect long-range chromatin interactions, allows extensive genome-wide investigation of 3D chromatin structure. However, broad application of Hi-C data have been hindered by the level of complexity in processing Hi-C data and the large size of raw sequencing data. In order to overcome these limitations, we constructed a database named 3DIV (a 3D-genome Interaction Viewer and database) that provides a list of long-range chromatin interaction partners for the queried locus with genomic and epigenomic annotations. 3DIV is the first of its kind to collect all publicly available human Hi-C data to provide 66 billion uniformly processed raw Hi-C read pairs obtained from 80 different human cell/tissue types. In contrast to other databases, 3DIV uniquely provides normalized chromatin interaction frequencies against genomic distance dependent background signals and a dynamic browsing visualization tool for the listed interactions, which could greatly advance the interpretation of chromatin interactions. '3DIV' is available at http://kobic.kr/3div.


Assuntos
Cromatina/genética , Bases de Dados Genéticas , Genoma Humano , Software , Cromatina/ultraestrutura , Bases de Dados de Ácidos Nucleicos , Epigênese Genética , Estudo de Associação Genômica Ampla , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imageamento Tridimensional , Internet , Anotação de Sequência Molecular , Conformação de Ácido Nucleico , Polimorfismo de Nucleotídeo Único
13.
Biomedicines ; 12(9)2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39335596

RESUMO

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown efficacy in treating psoriasis, a chronic inflammatory skin disease affecting 1-3% of the global population; however, the mechanisms remain unclear. This study investigated CBD's effects on imiquimod (IMQ)-induced psoriasis in mice, which were divided into five groups: Control, IMQ, Clobetasol, 0.01% CBD, and 0.1% CBD. After inducing psoriasis with IMQ, clobetasol or CBD was applied. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), with histopathological changes examined via hematoxylin and eosin staining. Gene expression of inflammatory markers (Il1b, Il6, Il12b, Il17a, Il22, and Tnf) was analyzed by RT-PCR, while protein levels of signal transducer and activator of transcription (STAT)3, P-STAT3, Janus kinase (JAK)2, and JAK3 were evaluated through western blot and immunohistochemistry. The results demonstrated that CBD significantly reduced PASI scores, epidermal thickness, keratosis, hyperproliferation, and inflammation. Moreover, CBD inhibited the IL-23 receptor-mediated JAK2-STAT3 signaling pathway, leading to the downregulation of Il1b, Il6, Il12b, Il17a, Il22, and Tnf expression. These findings suggest that CBD effectively alleviates psoriasis-like symptoms in mice and may serve as a promising therapeutic agent for psoriasis by targeting the JAK2-STAT3 pathway.

14.
Transl Vis Sci Technol ; 13(5): 18, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776108

RESUMO

Purpose: We aimed to design, develop, and evaluate an internet of things-enabled patch (IoT patch) for real-time remote monitoring of adherence (or patch wear time) during patch treatment in child participants in clinical trials. This study provides healthcare providers with a tool for objective, real-time, and remote assessment of adherence and for making required adjustments to treatment plans. Methods: The IoT patch had two temperature microsensors and a wireless chip. One sensor was placed closer to the skin than the other, resulting in a temperature difference depending on whether the patch was worn. When the patch was worn, it measured temperatures every 30 seconds and transmitted temperature data to a cloud server via a mobile application every 15 seconds. The patch was evaluated via 2 experiments with 30 healthy adults and 40 children with amblyopia. Results: Excellent monitoring accuracy was observed in both adults (mean delay of recorded time data, 0.4 minutes) and children (mean, 0.5 minutes). The difference between manually recorded and objectively recorded patch wear times showed good agreement in both groups. Experiment 1 showed accurate monitoring over a wide range of temperatures (from 0 to 30°C). Experiment 2 showed no significant differences in wearability (ease-of-use and comfort scores) between the IoT and conventional patches. Conclusions: The IoT patch offers an accurate, real-time, and remote system to monitor adherence to patch treatment. The patch is comfortable and easy to use. The utilization of an IoT patch may increase adherence to patch treatment based on accurate monitoring. Translational Relevance: Results show that the IoT patch can enable real-time adherence monitoring in clinical trials, improving treatment precision, and patient compliance to enhance outcomes.


Assuntos
Internet das Coisas , Tecnologia sem Fio , Humanos , Feminino , Masculino , Adulto , Criança , Tecnologia sem Fio/instrumentação , Cooperação do Paciente , Desenho de Equipamento/métodos , Pré-Escolar , Adulto Jovem , Dispositivos Eletrônicos Vestíveis , Tecnologia de Sensoriamento Remoto/instrumentação , Tecnologia de Sensoriamento Remoto/métodos
15.
Cell Rep ; 43(8): 114558, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39088321

RESUMO

Chromatin priming promotes cell-type-specific gene expression, lineage differentiation, and development. The mechanism of chromatin priming has not been fully understood. Here, we report that mouse hematopoietic stem and progenitor cells (HSPCs) lacking the Baf155 subunit of the BAF (BRG1/BRM-associated factor) chromatin remodeling complex produce a significantly reduced number of mature blood cells, leading to a failure of hematopoietic regeneration upon transplantation and 5-fluorouracil (5-FU) injury. Baf155-deficient HSPCs generate particularly fewer neutrophils, B cells, and CD8+ T cells at homeostasis, supporting a more immune-suppressive tumor microenvironment and enhanced tumor growth. Single-nucleus multiomics analysis reveals that Baf155-deficient HSPCs fail to establish accessible chromatin in selected regions that are enriched for putative enhancers and binding motifs of hematopoietic lineage transcription factors. Our study provides a fundamental mechanistic understanding of the role of Baf155 in hematopoietic lineage chromatin priming and the functional consequences of Baf155 deficiency in regeneration and tumor immunity.


Assuntos
Diferenciação Celular , Cromatina , Hematopoese , Células-Tronco Hematopoéticas , Animais , Cromatina/metabolismo , Camundongos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Camundongos Endogâmicos C57BL , Regeneração , Fluoruracila/farmacologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
16.
Thyroid ; 34(1): 112-122, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38009221

RESUMO

Background: Although recent studies have introduced antibiotics as a potential risk factor for thyroid cancer, further studies are necessary. We examined the association between long-term antibiotic usage and thyroid cancer risk. Methods: This nationwide cohort study investigated 9,804,481 individuals aged 20 years or older who participated in health screening (2005-2006) with follow-up ending on December 31, 2019, using the Korean National Health Insurance Service database. Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for thyroid cancer risk according to the cumulative days of antibiotic prescription and the number of antibiotic classes, respectively. A 1:1 propensity score (PS) matching was also performed for analysis. Results: Compared with nonusers of antibiotics, participants prescribed ≥365 days of antibiotics showed an increased risk of thyroid cancer (aHR, 1.71; CI, 1.66-1.78) after adjusting for covariates including age, smoking status, comorbidities including thyroid-related diseases, and the number of head and neck computed tomography scans. Participants prescribed ≥365 days of antibiotics also had a significantly increased risk of thyroid cancer (aHR, 1.37; CI, 1.34-1.40) compared with participants prescribed 1-14 days of antibiotics. Association remained significant in the 1:1 PS-matched cohort. Moreover, compared with nonusers of antibiotics, the 5 or more antibiotic class user group had a higher thyroid cancer risk (aHR, 1.71; CI, 1.65-1.78). Conclusions: Long-term antibiotic prescriptions and an increasing number of antibiotic classes may be associated with a higher risk of thyroid cancer in a duration-dependent manner. The effects of long-term antibiotic exposure on thyroid cancer should be further investigated.


Assuntos
Doenças da Glândula Tireoide , Neoplasias da Glândula Tireoide , Humanos , Estudos de Coortes , Neoplasias da Glândula Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/epidemiologia , República da Coreia/epidemiologia , Fatores de Risco , Antibacterianos/efeitos adversos , Estudos Retrospectivos
17.
Sci Rep ; 14(1): 22159, 2024 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333557

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, and the presence of glioma stem cells (GSCs) has been linked to its resistance to treatments and recurrence. Additionally, aberrant glycosylation has been implicated in the aggressiveness of cancers. However, the influence and underlying mechanism of N-glycosylation on the GSC phenotype and GBM malignancy remain elusive. Here, we performed an in-silico analysis approach on publicly available datasets to examine the function of N-glycosylation-related genes in GSCs and gliomas, accompanied by a qRT-PCR validation experiment. We found that high α-1,2-mannosidase MAN1C1 is associated with immunological functions and worse survival of glioma patients. Differential gene expression analysis and qRT-PCR validation revealed that MAN1C1 is highly expressed in GSCs. Furthermore, higher MAN1C1 expression predicts worse outcomes in glioma patients. Also, MAN1C1 expression is increased in the perinecrotic region of GBM and is associated with immunological and inflammatory functions, a hallmark of the GBM mesenchymal subtype. Further analysis confirmed that MAN1C1 expression is closely associated with infiltrating immune cells and disrupted immune response in the GBM microenvironment. These suggest that MAN1C1 is a potential biomarker for gliomas and may be important as an immunotherapeutic target for GBM.


Assuntos
Neoplasias Encefálicas , Glioma , Manosidases , Células-Tronco Neoplásicas , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/imunologia , Prognóstico , Manosidases/metabolismo , Manosidases/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Glioma/imunologia , Glioma/patologia , Glioma/genética , Glioma/metabolismo , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/imunologia , Glioblastoma/mortalidade , Masculino , Feminino , Glicosilação
18.
Sci Adv ; 10(4): eadj3880, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38266092

RESUMO

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here, we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. Increased TSP-1 abundance persists even after transient early-life heat stress. Such regulation requires CBP-1, a histone acetyltransferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers marked C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity.


Assuntos
Experiências Adversas da Infância , Proteínas de Caenorhabditis elegans , Resiliência Psicológica , Adulto , Humanos , Animais , Longevidade , Trombospondina 1 , Caenorhabditis elegans , Tetraspaninas/genética , Fatores de Transcrição , Proteínas de Caenorhabditis elegans/genética , Histona Acetiltransferases
19.
Genes Genomics ; 46(8): 881-898, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38847972

RESUMO

BACKGROUND: Since most of the commonly known oral diseases are explained in link with balance of microbial community, an accurate bacterial taxonomy profiling for determining bacterial compositional network is essential. However, compared to intestinal microbiome, research data pool related to oral microbiome is small, and general 16S rRNA screening method has a taxonomy misclassification issue in confirming complex bacterial composition at the species level. OBJECTIVE: Present study aimed to explore bacterial compositional networks at the species level within saliva of 39 oral disease patients (Dental Caries group: n = 26 and Periodontitis group: n = 13) through comparison with public Korean-specific healthy oral microbiome data. METHODS: Here, we applied comprehensive molecular diagnostics based on qRT-PCR and Sanger sequencing methods to complement the technical limitations of NGS-based 16S V3-V4 amplicon sequencing technology. RESULTS: As a result of microbiome profiling at the genus level, relative frequencies of many nitrate-reducing bacteria within each oral disease group were found to be significantly low compared to the healthy group. In addition, the molecular diagnostics-based bacterial identification method allowed the determination of the correct taxonomy of screened primary colonizers (Streptococcus and Actinomyces unclassification clusters) for each oral disease. Finally, as with the results of microbiome profiling at the genus level, many core-species classified within the saliva of each oral disease group were also related to nitrate-reduction, and it was estimated that various pathogens associated with each disease formed a bacterial network with the core-species. CONCLUSION: Our study introduced a novel approach that can compensate for the difficulty of identifying an accurate bacterial compositional network at the species level due to unclear taxonomy classification by using the convergent approach of NGS-molecular diagnostics. Ultimately, we suggest that our experimental approach and results could be potential reference materials for researchers who intend to prevent oral disease by determining the correlation between oral health and bacterial compositional network according to the changes in the relative frequency for nitrate-reducing species.


Assuntos
Microbiota , RNA Ribossômico 16S , Saliva , Humanos , Saliva/microbiologia , RNA Ribossômico 16S/genética , Feminino , Masculino , Microbiota/genética , Adulto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Pessoa de Meia-Idade , Cárie Dentária/microbiologia , Cárie Dentária/diagnóstico , Periodontite/microbiologia , Periodontite/diagnóstico , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação
20.
Micromachines (Basel) ; 14(12)2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38138325

RESUMO

Red phosphorus (rP) is one of the most promising anode materials for lithium-ion batteries, owing to its high theoretical capacity. However, its low electronic conductivity and large volume expansion during cycling limit its practical applications, as it exhibits low electrochemical activity and unstable cyclability. To address these problems, tellurium (Te)-rP-C composites, which have active materials (Te, rP) that are uniformly distributed within the carbon matrix, were fabricated through a simple high-energy ball milling method. Among the three electrodes, the Te-rP (1:2)-C electrode with a 5% FEC additive delivers a high initial CE of 80% and a high reversible capacity of 734 mAh g-1 after 300 cycles at a current density of 100 mA g-1. Additionally, it exhibits a high-rate capacity of 580 mAh g-1 at a high current density of 10,000 mA g-1. Moreover, a comparison of the electrolytes with and without the 5% FEC additive demonstrated improved cycling stability when the FEC additive was used. Ex situ XRD analysis demonstrated the lithiation/delithiation mechanism of Te-rP (1:2)-C after cycling based on the cyclic voltammetry results. Based on the electrochemical impedance spectroscopy analysis results, a Te-rP-C composite with its notable electrochemical performance as an anode can sufficiently contribute to the battery anode industry.

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