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1.
Clin Immunol ; 263: 110219, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631594

RESUMO

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.

2.
Food Funct ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651948

RESUMO

Background: Frailty has been one of the most serious global public health challenges we will ever face. Oxidative stress is associated with the pathogenesis of frailty, and may be accurately reflected by the oxidative balance score (OBS). However, there have been no studies examining the effect of OBS on frailty. Therefore, we aimed to explore the association between OBS and frailty and whether there was an interaction between the outcomes. Methods: 22 914 participants aged over 20 years taking part in the National Health and Nutrition Examination Survey (NHANES) in 2007-2018 were involved in the study. Sixteen dietary factors and four lifestyle factors were selected to score the OBS. A modified 36-item deficit cumulative frailty index (FI) was used to assess the degree of frailty. The association between OBS and frailty was analyzed using binary logistic regression. Subgroup analysis and interaction tests were used to investigate whether this association was stable across populations. Results: A negative association between OBS and the prevalence of frailty was found in this study. There was also an interaction between OBS and age in their association with frailty. High OBS was significantly and negatively associated with the prevalence of frailty in the 20-39 and 40-64 age groups. In addition, higher OBS combined with a population in the 20-39 age group resulted in a stronger negative association with frailty. Conclusion: High OBS was significantly associated with lower odds of frailty. An interaction existed between OBS and age. Individuals, especially in relatively young populations, are advised to increase OBS through greater intake of antioxidant nutrients and healthier lifestyles, thereby reducing the adverse effects of frailty.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38584217

RESUMO

PURPOSE: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. METHODS: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. RESULTS: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. CONCLUSION: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision.

4.
Front Oncol ; 14: 1356250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515581

RESUMO

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.

5.
J Hazard Mater ; 469: 133992, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38460262

RESUMO

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent anthropogenic chemicals that are widely distributed in the environment and pose significant risks to human health. Foam fractionation has emerged as a promising method to recover PFOS/PFOA from water. However, PFOS/PFOA concentrations in wastewater are often inadequate to generate stable foams due to their high critical micelle concentrations and the addition of a cosurfactant is necessary. In this study, we developed whey soy protein (WSP) as a green frother and collector derived from soybean meal (SBM), which is an abundant and cost-effective agro-industrial residue. WSP exhibited excellent foaming properties across a wide pH range and demonstrated strong collection capabilities that enhanced the recovery of PFOS/PFOA. The mechanism underlying this collection ability was elucidated through various methods, revealing the involvement of electrostatic attraction, hydrophobic interaction, and hydrogen bonding. Furthermore, we designed a double plate internal to improve the enrichment of PFOS/PFOA by approximately 2.3 times while reducing water recovery. Under suitable conditions (WSP concentration: 300 mg/L, pH: 6.0, air flowrate: 300 mL/min), we achieved high recovery percentages of 94-98% and enrichment ratios of 7.5-12.8 for PFOS/PFOA concentrations ranging from 5 to 20 mg/L. This foam fractionation process holds great promise for the treatment of PFOS/PFOA and other per- and polyfluoroalkyl substances.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Humanos , Água , Proteínas de Soja , Soro do Leite/química , Proteínas do Soro do Leite , Fluorocarbonos/análise , Caprilatos/análise , Ácidos Alcanossulfônicos/análise , Poluentes Químicos da Água/análise
6.
Phytomedicine ; 128: 155501, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38471318

RESUMO

BACKGROUND: The discovering of an osteoclast (OC) coupling active agent, capable of suppressing OC-mediated bone resorption while concurrently stimulating osteoblast (OB)-mediated bone formation, presents a promising strategy to overcome limitations associated with existing antiresorptive agents. However, there is a lack of research on active OC coupling agents. PURPOSE: This study aims to investigate the potential of Jiangu Formula (JGF) in inhibiting OCs while maintaining the OCOB coupling function. METHODS: The anti-osteoporosis efficacy of JGF was evaluated in osteoporosis models induced by ovariectomy in C57BL/6 mouse and SD rats. The effect of JGF on OCs was evaluated by detecting its capacity to inhibit OC differentiation and bone resorption in an in vitro osteoclastogenesis model induced by RANKL. The OCOB coupling activity of JGF was evaluated by measuring the secretion levels of OC-derived coupling factors, OB differentiation activity of MC3T3-E1 interfered with conditioned medium, and the effect of JGF on OC inhibition and OB differentiation in a C3H10T1/2-RAW264.7 co-culture system. The mechanism of JGF was studied by network pharmacology and validated using western blot, immunofluorescence (IF), and ELISA. Following that, the active ingredients of JGF were explored through a chemotype-assembly approach, activity evaluation, and LC-MS/MS analysis. RESULTS: JGF inhibited bone resorption in murine osteoporosis without compromising the OCOB coupling effect on bone formation. In vitro assays showed that JGF preserved the coupling effect of OC on OB differentiation by maintaining the secretion of OC-derived coupling factors. Network analysis predicted STAT3 as a key regulation point for JGF to exert anti-osteoporosis effect. Further validation assays confirmed that JGF upregulated p-STAT3(Ser727) and its regulatory factors IL-2 in RANKL-induced RAW264.7 cells. Moreover, 23 components in JGF with anti-OC activity identified by chemotype-assembly approach and verification experiments. Notably, six compounds, including ophiopogonin D, ginsenoside Re, ginsenoside Rf, ginsenoside Rg3, ginsenoside Ro, and ononin were identified as OC-coupling compounds. CONCLUSION: This study first reported JGF as an agent that suppresses bone loss without affecting bone formation. The potential coupling mechanism of JGF involves the upregulation of STAT3 by its regulators IL-2. Additionally, the chemotype-assembly approach elucidated the activity compounds present in JGF, offering a novel strategy for developing an anti-resorption agent that preserves bone formation.

7.
J Cell Physiol ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468464

RESUMO

GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis. We found that GINS1 was significantly upregulated in HCC tissues and cell lines, especially in HCC tissues with vascular invasion and HCC cell lines with highly metastatic properties. Additionally, high expression of GINS1 was positively correlated with the progressive clinical features of HCC patients, including tumor number (multiple), tumor size (>5 cm), advanced tumor stage, vascular invasion and early recurrence, suggesting that GINS1 upregulation was greatly involved in HCC metastasis. Moreover, Kaplan-Meier survival analysis revealed that high GINS1 expression predicted a poor prognosis. Both in vitro and in vivo, silencing of GINS1 inhibited proliferation, migration, invasion and metastasis, while overexpression of GINS1 induced opposite effects. Mechanistically, we found that ZEB1 was a crucial regulator of GINS1-induced epithelial-mesenchymal transition (EMT), and GINS1 promoted EMT and tumor metastasis through ß-catenin signaling. Overall, the present study demonstrated that GINS1 promoted ZEB1-mediated EMT and tumor metastasis via ß-catenin signaling in HCC.

8.
J Sleep Res ; : e14166, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414320

RESUMO

Despite the high prevalence and significant health burden of obstructive sleep apnea (OSA), its underlying pathophysiology remains incompletely understood. This comprehensive review explores the emerging connection between vitamin D deficiency and OSA, discusses potential mechanisms underlying this association, and explores the therapeutic implications of these findings. Recent research has consistently highlighted the high incidence of vitamin D deficiency among patients with OSA, which often occurs independently of geographical location. This suggests that factors beyond lack of sunlight exposure may be involved. This review also discusses how reduced vitamin D may be associated with more severe manifestations of OSA. In addition, it explores the potentiality of using vitamin D supplements as a therapeutic strategy for OSA, noting that some studies have found improvements in sleep quality and a reduction in OSA severity. Potential mechanisms are proposed, including the role of vitamin D deficiency in promoting inflammation, oxidative stress, hypoxia, impairing immune function, muscle function, and gene polymorphism of vitamin D receptors, all of which could contribute to the pathogenesis of obstructive sleep apnea. The paper underscores the need for future research to validate these observations, to determine optimal vitamin D supplementation dosage and duration, to explore potential side effects and risks, and to investigate potential interactions with other treatments.

9.
J Biol Chem ; 300(3): 105765, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367667

RESUMO

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique "basic patch" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals.


Assuntos
Lectinas Tipo C , Receptores Mitogênicos , Ácido Úrico , Humanos , Gota/metabolismo , Lectinas Tipo C/química , Lectinas Tipo C/imunologia , Receptores Mitogênicos/química , Receptores Mitogênicos/imunologia , Ácido Úrico/química , Ácido Úrico/imunologia , Domínios Proteicos , Cristalografia por Raios X , Imagem Individual de Molécula , Linhagem Celular
10.
Angew Chem Int Ed Engl ; 63(19): e202400343, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38323892

RESUMO

Lithium polysulfides (LiPSs) are pivotal intermediates involved in all the cathodic reactions in lithium-sulfur (Li-S) batteries. Elucidating the solvation structure of LiPSs is the first step for rational design of electrolyte and improving Li-S battery performances. Herein, we investigate the solvation structure of LiPSs and find that Li salt anions tend to enter the first solvation sheath of LiPSs and form contact ion pairs in electrolyte. The anion-involved solvation structure of LiPSs significantly influences the intrinsic kinetics of the sulfur redox reactions. In particular, the LiPS solvation structure modified by lithium bis(fluorosulfonyl)imide endows Li-S batteries with reduced polarization and enhanced rate performances under high sulfur areal loading and lean electrolyte volume conditions. This work updates the fundamental understanding of the solvation chemistry of LiPSs and highlights electrolyte engineering for promoting the performances of Li-S batteries.

11.
Environ Sci Ecotechnol ; 21: 100391, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38328510

RESUMO

The trade-off and synergy relationship of ecosystem services is an important topic in the current assessment. The value of each service provided by the ecosystem is substantially affected by human activities, and conversely, its changes will also affect the relevant human decisions. Due to varying trade-offs among ecosystem services and synergies between them that can either increase or decrease, it is difficult to optimize multiple ecosystem services simultaneously, making it a huge challenge for ecosystem management. This study firstly develops a global Gross Ecosystem Product (GEP) accounting framework. It uses remote sensing data with a spatial resolution of 1 km to estimate the ecosystem services of forests, wetlands, grasslands, deserts, and farmlands in 179 major countries in 2018. The results show that the range of global GEP values is USD 112-197 trillion, with an average value of USD 155 trillion (the constant price), and the ratio of GEP to gross domestic product (GDP) is 1.85. The trade-offs and the synergies among different ecosystem services in each continent and income group have been further explored. We found a correspondence between the income levels and the synergy among ecosystem services within each nation. Among specific ecosystem services, there are strong synergies between oxygen release, climate regulation, and carbon sequestration services. A trade-off relationship has been observed between flood regulation and other services, such as water conservation and soil retention services in low-income countries. The results will help clarify the roles and the feedback mechanisms between different stakeholders and provide a scientific basis for optimizing ecosystem management and implementing ecological compensation schemes to enhance human well-being.

12.
BMJ Open ; 14(2): e076579, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38423773

RESUMO

OBJECTIVES: Colorectal cancer (CRC) encompasses a spectrum of pathological types, each exhibiting distinct biological behaviours that challenge the conventional T-staging system's predictive efficiency. Thus, this study aims to explore the prognostic significance of the T stage across various CRC pathological types, seeking to unravel insights that could enhance prognostic assessment in this complex disease. STUDY DESIGN: We performed a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database for primary CRC cases from 2010 to 2017. SETTING: The SEER database, comprising data from various US regional and state cancer registries, identified 39 321 patients with CRC. Our analysis focused on the three most common CRC pathological types: adenocarcinoma (AC), mucinous adenocarcinoma (MC) and signet ring cell carcinoma (SR). PRIMARY OUTCOME MEASURES: The study used Cox regression models to evaluate how different pathological characteristics impact mortality risk in patients with CRC. Time-dependent receiver operating characteristic curves were also applied to assess the prognostic accuracy of various tumour node metastasis (TNM)/non-mucinous (NM) stages. RESULTS: We observed significant associations between T stage and mortality risk for patients with AC and MC. Notably, in comparison to those at T1 stage, patients with AC in the T4 stage demonstrated a 2.01-fold increase in mortality risk (HR=2.01, 95% CI: 1.89 to 2.15), while patients with MC at T4 stage showed a 1.42-fold increase (HR=1.42, 95% CI: 1.03 to 1.97). However, within the SR group, T stages did not independently impact survival, showing no significant distinction (HR=1.07, 95% CI: 0.59 to 1.95). Intriguingly, the traditional TNM staging systems demonstrated limited discriminatory power in predicting prognosis for patients with SR when compared with the more innovative NM staging systems. CONCLUSIONS: This study uncovers important insights about the prognostic significance of the T stage in different types of CRC, highlighting the need for personalised assessments based on specific histological subtypes.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Humanos , Prognóstico , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Colorretais/epidemiologia , Adenocarcinoma/patologia
13.
Medicine (Baltimore) ; 103(2): e36957, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38215151

RESUMO

Gastrointestinal (GI) cancers pose a significant challenge due to high prevalence and mortality. While advancements in detection and conventional treatments have been made, prognosis often remains poor, particularly for advanced-stage cancers. Immunotherapy has emerged as a transformative approach, leveraging the body immune system against cancer, including immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer. These modalities have shown promise, achieving sustained responses and improved survival in some patients. However, their efficacy in GI cancers is less pronounced, hindered by drug resistance mechanisms that are either intrinsic or acquired over time. This review examines the latest understanding of immunotherapy in GI cancers, focusing on ICIs, cancer vaccines, and adoptive cell transfer, along with their associated outcomes and limitations. It delves into the mechanisms behind drug resistance, including alterations in immune checkpoints, the immunosuppressive tumor microenvironment, and genetic/epigenetic changes. The role of the gut microbiome is also considered as an emerging factor in resistance. To combat drug resistance, strategies such as enhancing immune response, targeting the tumor microenvironment, and modulating resistance mechanisms are explored. The review underscores the potential of ferroptosis induction as a novel approach. Looking forward, it highlights the need for personalized immunotherapies, understanding the influence of the gut microbiome, and further exploration of ferroptosis in overcoming resistance. While challenges persist, the continuous evolution in GI cancer immunotherapy research promises innovative treatments that could significantly improve patient outcomes.


Assuntos
Vacinas Anticâncer , Neoplasias Gastrointestinais , Humanos , Vacinas Anticâncer/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Imunoterapia , Resistência a Medicamentos , Microambiente Tumoral
14.
Nanoscale Horiz ; 9(3): 479-486, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38258388

RESUMO

As the demand for increasingly varied types of 1-dimensional (1D) materials grows, there is a greater need for new methods to synthesize these types of materials in a simple and scalable way. Chemical exfoliation is commonly used to make 2-dimensional (2D) materials, often in a way that is both straightforward and suitable for making larger quantities, yet this method has thus far been underutilized for synthesizing 1D materials. In the few instances when chemical exfoliation has been used to make 1D materials, the starting compound has been a van der Waals material, thus excluding any structures without these weak bonds inherently present. We demonstrate here that ionically bonded crystals can also be chemically exfoliated to 1D structures by choosing KFeS2 as an example. Using chemical exfoliation, antiferromagnetic 1D nanoribbons can be yielded in a single step. The nanoribbons are crystalline and closely resemble the parent compound both in structure and in intrinsic antiferromagnetism. The facile chemical exfoliation of an ionically bonded crystal shown in this work opens up opportunities for the synthesis of both magnetic and non-magnetic 1D nanomaterials from a greater variety of starting structures.

15.
Int J Oncol ; 64(3)2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38240092

RESUMO

Gastric cancer is one of the most common malignancies and has relatively high morbidity and mortality rates. Exosomes are nanoscale extracellular vesicles that originate from a diverse array of cells and may be found throughout various bodily fluids. These vesicles are endogenous nanocarriers in their natural state with the unique ability to transport lipids, proteins, DNA and RNA. Exosomes contain DNA, RNA, proteins, lipids and other bioactive components that have crucial roles in the transmission of information and regulation of cell activities in gastric cancer. This paper begins with an exploration of the composition, formation and release mechanisms of exosomes. Subsequently, the role of exosomes in the tumor microenvironment is reviewed in terms of the immune cell population, nonimmune cell population and other factors. Finally, the current status and challenges of exosome­based research on the progression, diagnosis and therapeutic methods of gastric cancer are summarized. This holistic review offers insight that may guide future research directions for exosomes and potentially pave the way for novel therapeutic interventions in the management of gastric cancer.


Assuntos
Exossomos , Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Exossomos/metabolismo , Microambiente Tumoral , Neoplasias/patologia , RNA/metabolismo , Proteínas/metabolismo , DNA , Lipídeos
16.
BMC Public Health ; 24(1): 114, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191356

RESUMO

BACKGROUND: This study aimed to explore the association between ideal cardiovascular health metrics (ICVHM) and arthritis (AR), as well as the interactions of various indicators in ICVHM on AR in US adults. METHODS: We involved 17,041 participants who were interviewed by NHANES from 2011 to 2018. AR included osteoarthritis or degenerative arthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis and other arthritis (Other AR). Logistic regression was applied to analyze the association between AR and ICVHM. Mixed graphical model (MGM) was used to explore the interaction between variables in ICVHM. RESULTS: Higher ICVHM scores had a protective effect on AR. Compared to "≤1" score, the ORs of AR in participants with 2, 3, 4, and ≥5 were 0.586, 0.472, 0.259, and 0.130, respectively. Similar results were also found in different types of AR. ICVHM has a maximum area under the curve value of 0.765 and the interaction between blood pressure and total cholesterol was 0.43. CONCLUSIONS: ICVHM correlates significantly with AR and is better at identifying AR than individual indicators. ICVHM can be better improved by controlling the indicators with stronger interactions. Our findings provide guidance for promoting health factors, which have important implications for identification and prevention of AR.


Assuntos
Artrite , Sistema Cardiovascular , Adulto , Humanos , Inquéritos Nutricionais , Indicadores de Qualidade em Assistência à Saúde , Pressão Sanguínea
17.
Animal Model Exp Med ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38247322

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA), a malignancy that arises from biliary epithelial cells, has a dismal prognosis, and few targeted therapies are available. Aurora B, a key mitotic regulator, has been reported to be involved in the progression of various tumors, yet its role in CCA is still unclarified. METHODS: Human CCA tissues and murine spontaneous CCA models were used to assess Aurora B expression in CCA. A loss-of-function model was constructed in CCA cells to determine the role of Aurora B in CCA progression. Subcutaneous and liver orthotopic xenograft models were used to assess the therapeutic potential of Aurora B inhibitors in CCA. RESULTS: In murine spontaneous CCA models, Aurora B was significantly upregulated. Elevated Aurora B expression was also observed in 62.3% of human specimens in our validation cohort (143 CCA specimens), and high Aurora B expression was positively correlated with pathological parameters of tumors and poor survival. Knockdown of Aurora B by siRNA and heteroduplex oligonucleotide (HDO) or an Aurora B kinase inhibitor (AZD1152) significantly suppressed CCA progression via G2/M arrest induction. An interaction between Aurora B and c-Myc was found in CCA cells. Targeting Aurora B significantly reduced this interaction and accelerated the proteasomal degradation of c-Myc, suggesting that Aurora B promoted the malignant properties of CCA by stabilizing c-Myc. Furthermore, sequential application of AZD1152 or Aurora B HDO drastically improved the efficacy of gemcitabine in CCA. CONCLUSIONS: Aurora B plays an essential role in CCA progression by modulating c-Myc stability and represents a new target for treatment and chemosensitization in CCA.

18.
Medicine (Baltimore) ; 103(1): e36867, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181239

RESUMO

We performed a bidirectional 2-sample Mendelian randomization (MR) design to explore the causal relation between telomere length (TL) and colorectal polyps. Genome-wide association study summary data of TL and colorectal polyps were extracted from the IEU open genome-wide association study database. Single nucleotide polymorphisms were served as instrumental variables at the significance threshold of P < 5 × 10-8. The inverse variance weighted method, MR-Egger method, and weight median method were performed for causal estimation in MR. Cochran Q test, MR-Egger intercept test, and leave-one-out analyses were performed to evaluate the pleiotropy of the MR results. One hundred and twenty-four single nucleotide polymorphisms were selected as instrumental variables. We found significant casual association between TL and colorectal polyps. Long TL increased the risk of colorectal polyps using the inverse variance weighted method [ukb-a-521: odds ratio (OR): 1.004, 95% confidence interval (CI): 1.001-1.007, P = .004; ukb-d-D12: OR: 1.008, CI: 1.004-1.012, P < .001; finn-b-CD2_BENIGN_COLORECANI_EXALLC2: OR: 1.170, CI: 1.027-1.332, P = .018]. Sensitivity analyses validated that the causality between TL and colorectal polyps was robust. The study provided a causal association between TL and colorectal polyps which indicated that TL might be served as a potential biomarker of colorectal polyps for screening and prevention. Nonetheless, the conclusions need further validation.


Assuntos
Pólipos do Colo , Humanos , Pólipos do Colo/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Causalidade , Telômero
19.
BMC Public Health ; 24(1): 57, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166928

RESUMO

BACKGROUND: Gastric cancer has attracted widespread attention on social media due to its high incidence and severity. The Bilibili, TikTok, and YouTube video-sharing platforms have received considerable interest among general health consumers. Nevertheless, it remains unclear whether the information in videos on these platforms is of satisfactory content and quality. METHODS: A total of 300 eligible videos related to gastric cancer were screened from three video-sharing platforms, Bilibili, TikTok, and YouTube, for assessment and analysis. First, the basic information presented in the videos was recorded. Next, we identified the source and content type of each video. Then, the Global Quality Scale (GQS), Journal of the American Medical Association (JAMA), and Modified DISCERN were used to assess the educational content and quality of each video. A comparative analysis was undertaken of the videos procured from these three sources. RESULTS: We identified six categories of uploaders of the 300 videos: 159 videos (53%) were uploaded by health professionals, 21 videos (7%) by users in science communications, 29 videos (9.67%) by general users, 27 videos (9%) from news agencies, 63 videos (12%) by nonprofit organizations, and one video (0.33%) by a for-profit organization. In terms of the content types of the 300 videos, we identified five distinct categories. There were 48 videos (16%) on early signals, 12 videos (4%) on late symptoms, 40 videos (13.33%) on etiologies and causations, 160 videos (53.33%) on scientific introductions, and 40 videos (13.33%) on treatment methods. The overall quality of the videos was evaluated by the GQS, JAMA, and Modified DISCERN and was found to be medium, with scores of 2.6/5, 2.41/4, and 2.71/5 points, respectively. CONCLUSIONS: This innovative study demonstrates that videos on social media platforms can help the public learn about early signals, late symptoms, treatment methods, etiologies and causations, and scientific introductions of gastric cancer. However, both the content and quality of uploaded recordings are inadequate currently. More efforts should be made to enhance the content and quality of videos on gastric cancer and to increase public awareness.


Assuntos
Mídias Sociais , Neoplasias Gástricas , Estados Unidos , Humanos , Neoplasias Gástricas/diagnóstico , Comunicação , Escolaridade , Pessoal de Saúde , Reprodutibilidade dos Testes , Gravação em Vídeo , Disseminação de Informação
20.
Sci Rep ; 14(1): 2392, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287035

RESUMO

The overall picture of degloving skin and soft tissue injuries (DSTI) remains a blank space in China. Therefore, a retrospective study was designed to summarize the current situation of this injury. Patients diagnosed with DSTI hospitalized between 2013 and 2018 were identified from the Hospital Quality Monitoring System (HQMS) database, of whom demographics, injury characteristics, hospitalization and cost information were analyzed. A total of 62,709 patients were enrolled in this study. Male sex predominated, with a mean age of 43.01 ± 19.70 years. Peasants seemed to be the most vulnerable. East China and Hubei province had the most patients. The most and least frequently injured anatomic site were lower extremity and torso, respectively. Traffic-related accidents and summer accounted for the highest proportion in terms of injury mechanism and season. The operation rate of DSTI roughly showed a growing trend, and the average length of stay was 22.02 ± 29.73 days. At discharge, 0.93% of DSTI patients ended up in death. Medicine accounted mostly for hospitalization cost, while the proportion decreased year by year. More than half DSTI patients paid at their own charge. This study made a relatively detailed description of DSTI patients nationwide, and might provide enlightenments for better prevention and treatment.


Assuntos
Pacientes Internados , Lesões dos Tecidos Moles , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Hospitalização , Pele , Lesões dos Tecidos Moles/epidemiologia , Lesões dos Tecidos Moles/cirurgia
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