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The nanostructure of Nafion and poly(vinylidene fluoride) (PVDF) blend membranes is successfully aligned through a mechanical uniaxial stretching method. The phase-separated morphology of Nafion molecules distinctly forms hydrophilic proton channels with increased connectivity, resulting in enhanced proton conductivity. Additionally, the crystalline phase of PVDF molecules undergoes a successful transformation from the α- to ß-phase during membrane stretching, demonstrating an alignment of fluorine and hydrogen atoms with a TTTT(trans) structure. The aligned nanostructure of the blend film, combined with the dipole polarization of the ß-phase PVDF, synergistically enhances the proton conduction through the membrane for operating proton-exchange membrane fuel cells (PEMFCs). The controlled structures of the blend membranes are thoroughly investigated using atomic force microscopy and small-angle X-ray scattering. Furthermore, the improved in-plane proton conductivity facilitates increased proton conduction at the interface between the membrane and catalyst layer in the membrane-electrode assembly, ultimately enhancing the power generation of PEMFCs.
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Tungsten oxide (WO3) is known for its photochromic properties, making it useful for smart windows, displays, and sensors. However, its small bandgap leads to rapid recombination of electron-hole pairs, resulting in poor photochromic performance. This study aims to enhance the photochromic properties of WO3 by synthesizing hexagonal tungsten oxide via hydrothermal synthesis, which increases surface area and internal hydrates. Titanium oxide (TiO2) was adsorbed onto the tungsten oxide to inject additional charges and reduce electron-hole recombination. Additionally, polyvinylpyrrolidone (PVP) was used to improve dispersion in organic solvents, allowing for the fabrication of high-quality films using the doctor blade method. Characterization confirmed the enhanced surface area, crystal structure, and dispersion stability. Reflectance and transmittance measurements demonstrated significant improvements in photochromic properties due to the composite structure. These findings suggest that the introduction of TiO2 and PVP to tungsten oxide effectively enhances its photochromic performance, broadening its applicability in various advanced photochromic applications.
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Recently, the need to develop a robust three-dimensional (3D) cell culture system that serves as a valuable in vitro tumor model has been emphasized. This system should closely mimic the tumor growth behaviors observed in vivo and replicate the key elements and characteristics of human tumors for the effective discovery and development of anti-tumor therapeutics. Therefore, in this study, we developed an effective 3D in vitro model of human prostate cancer (PC) using a marine collagen-based biomimetic 3D scaffold. The model displayed distinctive molecular profiles and cellular properties compared with those of the 2D PC cell culture. This was evidenced by (1) increased cell proliferation, migration, invasion, colony formation, and chemoresistance; (2) upregulated expression of crucial multidrug-resistance- and cancer-stemness-related genes; (3) heightened expression of key molecules associated with malignant progressions, such as epithelial-mesenchymal transition transcription factors, Notch, matrix metalloproteinases, and pluripotency biomarkers; (4) robust enrichment of prostate cancer stem cells (CSCs); and (5) enhanced expression of integrins. These results suggest that our 3D in vitro PC model has the potential to serve as a research platform for studying PC and prostate CSC biology, as well as for screening novel therapies targeting PC and prostate CSCs.
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Antineoplásicos , Proliferação de Células , Colágeno , Células-Tronco Neoplásicas , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/efeitos dos fármacos , Técnicas de Cultura de Células em Três Dimensões/métodos , Animais , Movimento Celular/efeitos dos fármacos , Alicerces Teciduais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Organismos Aquáticos , Descoberta de Drogas/métodosRESUMO
Extensive research has explored the functional correlation between stem cells and progenitor cells, particularly in blood. Hematopoietic stem cells (HSCs) can self-renew and regenerate tissues within the bone marrow, while stromal cells regulate tissue function. Recent studies have validated the role of mammalian stem cells within specific environments, providing initial empirical proof of this functional phenomenon. The interaction between bone and blood has always been vital to the function of the human body. It was initially proposed that during evolution, mammalian stem cells formed a complex relationship with the surrounding microenvironment, known as the niche. Researchers are currently debating the significance of molecular-level data to identify individual stromal cell types due to incomplete stromal cell mapping. Obtaining these data can help determine the specific activities of HSCs in bone marrow. This review summarizes key topics from previous studies on HSCs and their environment, discussing current and developing concepts related to HSCs and their niche in the bone marrow.
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Medula Óssea , Células-Tronco Hematopoéticas , Nicho de Células-Tronco , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Nicho de Células-Tronco/fisiologia , Animais , Medula Óssea/metabolismo , Medula Óssea/fisiologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologiaRESUMO
The association between leukemic stem cells (LSCs) and leukemia development has been widely established in the context of genetic alterations, epigenetic pathways, and signaling pathway regulation. Hematopoietic stem cells are at the top of the bone marrow hierarchy and can self-renew and progressively generate blood and immune cells. The microenvironment, niche cells, and complex signaling pathways that regulate them acquire genetic mutations and epigenetic alterations due to aging, a chronic inflammatory environment, stress, and cancer, resulting in hematopoietic stem cell dysregulation and the production of abnormal blood and immune cells, leading to hematological malignancies and blood cancer. Cells that acquire these mutations grow at a faster rate than other cells and induce clone expansion. Excessive growth leads to the development of blood cancers. Standard therapy targets blast cells, which proliferate rapidly; however, LSCs that can induce disease recurrence remain after treatment, leading to recurrence and poor prognosis. To overcome these limitations, researchers have focused on the characteristics and signaling systems of LSCs and therapies that target them to block LSCs. This review aims to provide a comprehensive understanding of the types of hematopoietic malignancies, the characteristics of leukemic stem cells that cause them, the mechanisms by which these cells acquire chemotherapy resistance, and the therapies targeting these mechanisms.
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Neoplasias Hematológicas , Células-Tronco Neoplásicas , Humanos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Hematopoéticas/metabolismo , Leucemia/patologia , Leucemia/genética , Leucemia/metabolismo , Transdução de Sinais , Animais , Microambiente Tumoral/genética , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética , MutaçãoRESUMO
PURPOSE: The efficacy of exercise in men with prostate cancer (PCa) on active surveillance (AS) remains unclear. In this meta-analysis, we aimed to examine the effects of exercise in PCa patients on AS. METHODS: A literature search was conducted in PubMed, EMBASE, and the Cochrane Library using search terms, including exercise, PCa, AS, and randomized controlled trials (RCTs). The means and standard deviations for peak oxygen consumption (VO2peak), prostate-specific antigen (PSA) levels, and quality of life (QoL) were extracted for the intervention and control groups. A random-effects model was used to summarize the effects of exercise. RESULTS: Of the 158 identified studies, six RCTs with 332 patients were included. The interventions included lifestyle modifications (aerobic exercise + diet) in three studies and different exercise modalities in three studies. The intervention duration was 2-12 months; three interventions were supervised and three were self-directed. The pooled weighted mean difference between exercise and usual care for VO2peak was 1.42 mL/kg/min (95% confidence interval [CI]: 0.30 to 2.54, P ≤ 0.001). A non-significant effect was observed for QoL (pooled standardized mean difference [SMD]: 0.24, 95% CI: - 0.03 to 0.51, P = 0.08) which became statistically significant and stronger after excluding one outlier study (P < 0.001). Exercise also had a positive effect on PSA levels (pooled SMD: - 0.43, 95% CI: - 0.87 to 0.01, P = 0.05). CONCLUSION: Exercise improves cardiorespiratory fitness and may improve QoL and PSA levels in men with PCa on AS. Further studies with larger sample sizes are warranted to obtain more reliable results.
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Antígeno Prostático Específico , Neoplasias da Próstata , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Masculino , Antígeno Prostático Específico/sangue , Consumo de Oxigênio/fisiologia , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Conduta Expectante/métodosRESUMO
Cancer vasculogenesis is a pivotal focus of cancer research and treatment given its critical role in tumor development, metastasis, and the formation of vasculogenic microenvironments. Traditional approaches to investigating cancer vasculogenesis face significant challenges in accurately modeling intricate microenvironments. Recent advancements in three-dimensional (3D) bioprinting technology present promising solutions to these challenges. This review provides an overview of cancer vasculogenesis and underscores the importance of precise modeling. It juxtaposes traditional techniques with 3D bioprinting technologies, elucidating the advantages of the latter in developing cancer vasculogenesis models. Furthermore, it explores applications in pathological investigations, preclinical medication screening for personalized treatment and cancer diagnostics, and envisages future prospects for 3D bioprinted cancer vasculogenesis models. Despite notable advancements, current 3D bioprinting techniques for cancer vasculogenesis modeling have several limitations. Nonetheless, by overcoming these challenges and with technological advances, 3D bioprinting exhibits immense potential for revolutionizing the understanding of cancer vasculogenesis and augmenting treatment modalities.
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Obesity is a potential risk factor for meniscal tear (MT). We utilized meta-analysis of observational studies and Mendelian randomization (MR) analyses to elucidate the association between body mass index (BMI) and MT. In meta-analysis, a search was performed on June 27, 2022, using PubMed and Embase databases. Odds ratios and 95% confidence intervals were extracted from included studies. In MR analyses, the research utilized summary-level data on BMI and MT obtained from Genetic Investigation of Anthropometric Traits and the FinnGen Consortium, respectively. In meta-analysis, four studies comprising 826,383 participants were included. The pooled odds ratio of MT in the high BMI group was 1.32 (95% confidence interval, 0.83-2.09), compared with the nonhigh BMI group. The pooled odds ratio in the under 30 group was 1.76 (95% confidence interval, 0.61-5.03). In MR analyses, one standard deviation increase in genetically predicted BMI was associated with meniscus derangement as a chronic subtype of MT (odds ratio, 1.36; 95% confidential interval, 1.17-1.59). We found that a high BMI was not associated with an increased likelihood of MT based on meta-analysis of observational studies; however, by complementing MR analyses, we elucidated the causality of BMI increase on meniscus derangement as a chronic subtype of MT.
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Índice de Massa Corporal , Análise da Randomização Mendeliana , Obesidade , Estudos Observacionais como Assunto , Lesões do Menisco Tibial , Humanos , Lesões do Menisco Tibial/genética , Obesidade/genética , Fatores de RiscoRESUMO
Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.
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Camellia sinensis , Catequina , Humanos , Metabolismo Secundário , Éxons , Cromossomos Humanos Par 15 , Camellia sinensis/genética , CháRESUMO
Human papillomavirus (HPV) is a major causative factor of head and neck squamous cell carcinoma (HNSCC), and the incidence of HPV- associated HNSCC is increasing. The role of tumor microenvironment in viral infection and metastasis needs to be explored further. We studied the molecular characteristics of primary tumors (PTs) and lymph node metastatic tumors (LNMTs) by stratifying them based on their HPV status. Eight samples for single-cell RNA profiling and six samples for spatial transcriptomics (ST), composed of matched primary tumors (PT) and lymph node metastases (LNMT), were collected from both HPV- negative (HPV- ) and HPV-positive (HPV+ ) patients. Using the 10x Genomics Visium platform, integrative analyses with single-cell RNA sequencing were performed. Intracellular and intercellular alterations were analyzed, and the findings were confirmed using experimental validation and publicly available data set. The HPV+ tissues were composed of a substantial amount of lymphoid cells regardless of the presence or absence of metastasis, whereas the HPV- tissue exhibited remarkable changes in the number of macrophages and plasma cells, particularly in the LNMT. From both single-cell RNA and ST data set, we discovered a central gene, pyruvate kinase muscle isoform 1/2 (PKM2), which is closely associated with the stemness of cancer stem cell-like populations in LNMT of HPV- tissue. The consistent expression was observed in HPV- HNSCC cell line and the knockdown of PKM2 weakened spheroid formation ability. Furthermore, we found an ectopic lymphoid structure morphology and clinical effects of the structure in ST slide of the HPV+ patients and verified their presence in tumor tissue using immunohistochemistry. Finally, the ephrin-A (EPHA2) pathway was detected as important signals in angiogenesis for HPV- patients from single-cell RNA and ST profiles, and knockdown of EPHA2 declined the cell migration. Our study described the distinct cellular composition and molecular alterations in primary and metastatic sites in HNSCC patients based on their HPV status. These results provide insights into HNSCC biology in the context of HPV infection and its potential clinical implications.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Papillomavirus Humano , Papillomaviridae/genética , Neoplasias de Cabeça e Pescoço/genética , Perfilação da Expressão Gênica/métodos , RNA , Microambiente Tumoral/genéticaRESUMO
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting the voluntary motor nervous system. Several observational studies have provided conflicting results regarding the association between smoking and ALS. Therefore, our objective was to investigate this association through a systematic review, meta-analysis, and dose-response analysis. METHODS: On 16 January 2023, we initially extracted records from medical databases, which included Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included case-control and cohort studies as eligible studies. Subgroup analyses were performed based on sex, study design, and current smoking. Restricted cubic-spline analysis was utilized to assess the dose-response relationship between smoking (pack-years) and ALS. RESULTS: Twenty-eight case-control and four cohort studies met the inclusion criteria. The unadjusted OR for the overall association between smoking and ALS was 1.14 (95% CI: 1.06-1.22, I2=44%, p<0.001), and the adjusted OR (AOR) was 1.12 (95% CI: 1.03-1.21, I2=49%, p=0.009). Subgroup analysis revealed a more pronounced association among current smokers, with an AOR of 1.28 (95% CI: 1.10-1.49, I2=66%, p<0.001) and AOR of 1.28 (95% CI: 1.10-1.48, I2=58%, p=0.001). In the dose-response analysis, the non-linear model revealed an inverted U-shaped curve. CONCLUSIONS: Our study provides evidence of a positive relationship between smoking and the risk of ALS. To mitigate the risk of developing ALS, discontinuing smoking, which is a modifiable risk factor, may be crucial.TRIAL REGISTRATION: The study was registered in PROSPERO.IDENTIFIER: CRD42023388822.
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Graphitic carbon-coated ZnPS3 is prepared via direct phosphosulfurization and high energy mechanical milling (HEMM) with multiwall carbon nanotubes (MWCNTs) and first introduced as an anode for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). The HEMM process with MWCNTs reduces the particle size of as-synthesized ZnPS3 bulk to 100-500 nm and yields the ≈5 nm thick graphitic carbon coated ZnPS3 nanoparticles, which are the nanocomposites of 5 nm sized nanocrystallites embedded in the amorphous matrix. The ZnPS3 electrode undergoes the combined conversion and alloying reactions with Li and Na ions and exhibits high initial discharge and charge capacities in both LIBs and SIBs. The graphitic carbon-coated ZnPS3 electrode exhibits excellent high-rate capability and long-term cyclability. The superior electrochemical properties can be attributed to high electrical conductivity, high Li ion mobility, and high reversibility and structural stability derived from the graphitic carbon-coated nanoparticles. This study demonstrates that the novel graphitic carbon-coated ZnPS3 is a promising anode material for both LIBs and SIBs and the graphitic carbon coating methodology by HEMM is expected to apply to the various metal oxides, sulfides, and phosphides.
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Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTß, IL-22R, RANK, LTßR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway. Furthermore, our study also revealed the cytoprotective effects of FCPs on TECs against cyclophosphamide-induced cellular injury through the NF-κB signaling pathway. Importantly, FCPs exhibited a significant capability to facilitate thymic regeneration in mice after cyclophosphamide-induced damage via the NF-κB pathway. Taken together, this study sheds light on the role of FCPs in TEC function, thymopoiesis, and thymic regeneration, providing greater insight into the development of novel therapeutic strategies for effective thymus repopulation for numerous clinical conditions in which immune reconstitution is required.
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NF-kappa B , Timócitos , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Citoproteção , Timo , Células Epiteliais , Colágeno/metabolismo , Expressão Gênica , Proliferação de Células , Ciclofosfamida/efeitos adversosRESUMO
In individuals with Alzheimer's disease, the brain exhibits elevated levels of IL-1ß and oxygenated cholesterol molecules (oxysterols). This study aimed to investigate the effects of side-chain oxysterols on IL-1ß expression using HMC3 microglial cells and ApoE-deficient mice. Treatment of HMC3 cells with 25-hydroxycholesterol (25OHChol) and 27-hydroxycholesterol (27OHChol) led to increased IL-1ß expression at the transcript and protein levels. Additionally, these oxysterols upregulated the surface expression of MHC II, a marker of activated microglia. Immunohistochemistry performed on the mice showed increased microglial expression of IL-1ß and MHC II when fed a high-cholesterol diet. However, cholesterol and 24s-hydroxycholesterol did not increase IL-1ß transcript levels or MHC II expression. The extent of IL-1ß increase induced by 25OHChol and 27OHChol was comparable to that caused by oligomeric ß-amyloid, and the IL-1ß expression induced by the oxysterols was not impaired by polymyxin B, which inhibited lipopolysaccharide-induced IL-1ß expression. Both oxysterols enhanced the phosphorylation of Akt, ERK, and Src, and inhibition of these kinase pathways with pharmacological inhibitors suppressed the expression of IL-1ß and MHC II. The pharmacological agents chlorpromazine and cyclosporin A also impaired the oxysterol-induced expression of IL-1ß and upregulation of MHC II. Overall, these findings suggest that dysregulated cholesterol metabolism leading to elevated levels of side-chain oxysterols, such as 25OHChol and 27OHChol, can activate microglia to secrete IL-1ß through a mechanism amenable to pharmacologic intervention. The activation of microglia and subsequent neuroinflammation elicited by the immune oxysterols can contribute to the development of neurodegenerative diseases.
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Microglia , Oxisteróis , Animais , Camundongos , Microglia/metabolismo , Oxisteróis/metabolismo , Doenças Neuroinflamatórias , Macrófagos/metabolismo , Encéfalo/metabolismoRESUMO
Hopping locomotion has the potential to enable small-scale robots to maneuver lands quickly while overcoming obstacles bigger than themselves. To make this possible, in this paper, we propose a novel design of a high-power linear actuator for a small-scale hopper. The key design principle of the linear actuator is to use a power spring and an active clutch. The power spring provides a near constant torque along the wide range of output displacement. The active clutch controls the moving direction and operation timing of the linear actuator, which enables the hopper to take off at the right timing. As a result, the hopper has a size of 143 mm, a mass of 45.9 g, and hops up to 0.58 m.
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Colorectal cancer (CRC) is a prevalent cancer worldwide, ranking as the third most common cancer and the second leading cause of cancer-related deaths. The presence or absence of lymph node metastases is one of the representative markers for predicting CRC prognosis, but often yields heterogeneous results. In this study, we conducted an integrative molecular analysis of CRC using publicly available data from The Cancer Genome Atlas database and NCBI's Gene Expression Omnibus. Through our analysis, we identified 372 upregulated genes that were differentially expressed in CRC patients. Additionally, Kyoto Encyclopedia of Genes and Genomes analysis revealed five significant pathways, including Hippo, FC-gamma, and forkhead box O signaling pathways, which are known to be associated with cancer. Survival analysis of 28 genes involved in these pathways led to the identification of 13 genes with prognostic significance (P < 0.05). To validate our findings, logistic regression models were generated and tested in multiple cohorts, demonstrating significant accuracy. Moreover, we identified six genes (BNIP3, CD63, RDX, RGCC, WASF1, and WASF3) whose combination predicted the best prognosis based on survival analysis. This predictive model holds promise as a potential biomarker for prognosis, survival, and treatment efficacy. In conclusion, our study provides valuable insights into the molecular characteristics of CRC and identifies prognostic biomarkers. The combination of differentially expressed genes and their involvement in cancer-related pathways enhances our understanding of CRC pathogenesis and opens avenues for personalized treatment approaches and improved patient outcomes.
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Background: While people's living standards are improving, the incidence of chronic diseases due to a lack of exercise is increasing. Complex health conditions (e.g., metabolic syndrome) are becoming common, and means to lower their incidence are essential. Methods: This study systematically reviewed the literature and performed a meta-analysis on the effects of Baduanjin exercise on metabolic syndrome-related factors. Using four English databases and three Chinese databases, randomized controlled trials on the effects of Baduanjin exercise on metabolic syndrome were identified. We analyzed whether Baduanjin could alleviate various metabolic syndrome indicators according to our selection guidelines. Results: We found that Baduanjin exercise had positive effects on blood pressure (systolic blood pressure: mean difference (MD)=-6.39; 95% confidence interval (CI): -9.86 to -2.92; I2=12%; diastolic blood pressure: MD=-2.86; 95% CI: -5.96 to -0.23; I2=35%; P=0.07) and total cholesterol (standardized mean (SMD)= -0.55; 95% CI: -1.11 to 0.02; I2=86%; P=0.06), triglyceride (SMD=-0.29; 95% CI: -1.13 to - 0.56; I2=94%; P<0.51), and low-density cholesterol (SMD =-0.33; 95% CI: -0.52 to -0.14; I2=0%; P<0.0007) levels. Conclusion: This evidence shows that Baduanjin exercise provides beneficial effects by improving metabolic syndrome and cardiovascular disease in adults. This suggests that Baduanjin exercise could be an effective alternative or complementary approach to conventional treatments for adults with metabolic problems. Additionally, these findings suggest that more rigorous randomized control trials are needed in the future.
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The expression of CD14 in monocytic cells is elevated in atherosclerotic lesions where 7-oxyterols are abundant. However, it remains unknown whether atheroma-relevant 7-oxysterols are involved in receptor expression. Therefore, we investigated the effects of 7α-hydroxycholesterol (7αOHChol), 7ß-hydroxycholesterol (7ßOHChol), and 7-ketocholesterol (7K) on CD14 levels in THP-1 cells. The three 7-oxysterols increased CD14 transcript levels at a distinct time point, elevated cellular CD14 protein levels, and promoted the release of soluble CD (sCD14) from THP-1 cells. Our data revealed that CD14 expression was most strongly induced after treatment with 7αOHChol. Moreover, 7αOHChol alone upregulated membrane-bound CD14 levels and enhanced responses to lipopolysaccharides, as determined by CCL2 production and monocytic cell migration. The 7-oxysterols also increased the gelatinolytic activity of MMP-9, and a cell-permeable, reversible MMP-9 inhibitor, MMP-9 inhibitor I, significantly impaired sCD14 release. These results indicate that 7-oxysterols differentially induce CD14 expression in vascular cells and contribute to the monocytic cell expression of CD14 via overlapping, but distinct, mechanisms.
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Oxisteróis , Placa Aterosclerótica , Humanos , Oxisteróis/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Hidroxicolesteróis/farmacologia , Hidroxicolesteróis/metabolismo , Monócitos/metabolismoRESUMO
White blood cells (WBCs) act as mediators of inflammatory responses and are commonly measured in hospitals. Although several studies have reported a relation between WBC count and mortality, no systematic review or meta-analysis has been conducted. This study aimed to identify an association between WBC count and mortality. We conducted a systematic search on Embase using keywords such as "white blood cell" and "mortality." We analyzed the hazard ratios (HRs) for WBC count of 1.0 × 109 cells/L regarding 2 criteria: the cause of mortality and the follow-up period. A total of 13 of 222 articles comprising a total of 62,904 participants were included in this study, meeting the criteria set. A positive association was observed between WBC count and mortality, as indicated by an HR of 1.10 (95% confidence interval [CI] 1.08 to 1.13). In additionally, WBC count emerged as a significant predictor of mortality in both groups, with an HR of 1.10 (95% CI 1.07 to 1.12) for patients with cardiovascular disease and an HR of 1.12 (95% CI 1.07 to 1.17) for the general population or patients with COVID-19. Furthermore, a higher WBC count demonstrated a significant association with long-term all-cause mortality (HR 1.09, 95% CI 1.07 to 1.12) and long-term cardiovascular mortality (HR 1.05, 95% CI 1.02 to 1.07). Similarly, a significant association was found between higher WBC count and short-term all-cause mortality (HR 1.12, 95% CI 1.09 to 1.16) and cardiovascular mortality (HR 1.12, 95% CI 1.07 to 1.17). Further research is necessary to explore the relation between WBC count and disease progression or death and to establish causality between elevated WBC count and disease progression.