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In the analytical process of spectrophotometry, the prerequisite for accurate qualitative and quantitative analysis is obtaining the intrinsic spectra of the analyte. However, the intrinsic properties of spectra can sometimes be masked by easily overlooked non-intrinsic factors, such as those from measuring instruments, leading to erroneous spectral identification. In this study, we documented an unusual redshift phenomenon in the far ultraviolet spectral region. With a spectrophotometer under the nitrogen atmosphere, we selected 14 representative inorganic anions and investigated their absorption spectral behaviors at different optical pathlengths and concentrations. It was intriguing to observe that the absorption peaks with maximum absorption wavelengths below a watershed wavelength of 200 nm underwent a redshift as pathlength and concentration increased, while those above 200 nm did not exhibit a significant redshift phenomenon. In-depth formula simulations and experimental verifications demonstrated that this peculiar spectral behavior was caused by unavoidable stray light in the spectrophotometer. Some methodological and instrumental recommendations are given in the paper. Our study results may serve as a reminder to carefully identify non-intrinsic phenomena when studying absorption spectra in the far ultraviolet region, and provide guidance on spectral corrections in scientific research and practical applications.
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Smoking is a well-established risk factor for several oral diseases, including oral cancer, oral leukoplakia and periodontitis, primarily related to reactive oxygen species (ROS). SS-31, a mitochondria-targeting tetrapeptide, has exhibited demonstrable efficacy in medical conditions by attenuating mitochondrial ROS production. However, its potential in the treatment of oral diseases remains underexplored. The aim of this study was to investigate the therapeutic potential of SS-31 in mitigating smoking-induced oral epithelial injury. Through in vitro experiments, our results indicate that SS-31 plays a protective role against cigarette smoke extract (CSE) by reducing oxidative stress, attenuating inflammatory response, and restoring mitochondrial function. Furthermore, we found that mitophagy, regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin (Parkin RBR E3 ubiquitin-protein ligase), was critical for the protective role of SS-31. Our findings offer valuable insights into SS-31's therapeutic potential in mitigating CSE-induced oxidative stress, inflammatory response, and mitochondrial dysfunction in oral epithelial cells. This study provides novel intervention targets for smoking-related oral diseases.
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Células Epiteliales , Mitocondrias , Mitofagia , Oligopéptidos , Estrés Oxidativo , Proteínas Quinasas , Humo , Ubiquitina-Proteína Ligasas , Estrés Oxidativo/efectos de los fármacos , Mitofagia/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Humanos , Proteínas Quinasas/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Oligopéptidos/farmacología , Ubiquitina-Proteína Ligasas/metabolismo , Humo/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Nicotiana/química , Nicotiana/efectos adversosRESUMEN
PURPOSE: To study the clinical and pathological characteristics of oral lichen planus (OLP) in a large sample. MATERIALS AND METHODS: A comprehensive analysis was conducted on 105 patients with oral lichen planus (OLP), considering various factors including sex, age, disease site, lesion type, lesion area, morphological characteristics, self-reported symptoms, and history of systemic diseases. Histopathological examination was performed for each patient, and the pathology results were analysed according to sex and age group. RESULTS: 70.5% of the OLP patients were female, and OLP was most likely to occur in the cheek, followed by the tongue, lips, gums and palate. The patients with moderate pain according to the VAS score accounted for 60%. Thirty-nine percent of the OLP patients had a systemic disease, and the most common clinical type of OLP was nonerosive. Most of the pathological results showed liquefaction degeneration of basal cells and infiltration of lamina propria lymphocytes. There was no statistically significant difference in pathological manifestations between male and female patients, and there were statistically significant differences in pathological manifestations among different ages patients. CONCLUSION: This study analysed the sociodemographic data and clinical manifestations of 105 OLP patients to guide follow-up treatment planning and disease monitoring. Moreover, pathological manifestations should be analysed to avoid delayed treatment and to monitor for carcinogenesis. Furthermore, the correlation of pathological manifestations among OLP patients with different sexes and ages is conducive to further research on the specific differential manifestations and possible underlying mechanisms involved.
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Liquen Plano Oral , Humanos , Liquen Plano Oral/patología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , China/epidemiología , Adulto Joven , Anciano de 80 o más Años , Adolescente , Factores de Edad , Factores Sexuales , Pueblos del Este de AsiaRESUMEN
The amino group is regarded as a multifunctional recognition group in fluorescent probes. It is nucleophilic, a strong electron-donating group and is a polar group with active hydrogen. Based on these characteristics, amino-based fluorescent probes combined with various fluorescent precursors have been constructed, with excellent sensing performance and low cytotoxicity. These probes have significant application value in the detection of food, living cells and organisms. Here, the relevant studies on amino fluorescent probes from 2016 to 2024 are systematically reviewed and their molecular design principles, recognition mechanisms and applications are described. These studies included 14 on exogenous and endogenous formaldehyde detection, five that detected polarity changes in the external environment and organelles in vivo, four intracellular mitochondrial and lysosomal viscosity detections, seven physiological environment and intracellular pH detections, seven metal ion detections in biological and environmental systems and four rapid detections of the hypochlorite anion (ClO-) in a variety of physiological processes and cells. The application scope of amino fluorescent probes is constantly expanding at present but, research progress in multiple application fields has not been summarized. This article mainly reviews the latest progress in amino fluorescent probes in the fields of food, the environment and the microenvironment, as well as looking forward to the development prospects of these fluorescent probes. Improving the reactivity of amino recognition groups and visual detection may become hot issues in future research.
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Osteoporosis is usually caused by excessive bone resorption and energy metabolism plays a critical role in the development of osteoporosis. However, little is known about the role of energy metabolism-related genes in osteoporosis. This study aimed to explore the important energy metabolism-related genes involved in the development of osteoporosis and develop a diagnosis signature for osteoporosis. The GSE56814, GSE62402, and GSE7158 datasets were downloaded from the NCBI Gene Expression Omnibus. The intersection of differentially expressed genes between high and low levels of body mineral density (BMD) and genes related to energy metabolism were screened as differentially expressed energy metabolism genes (DE-EMGs). Subsequently, a DE-EMG-based diagnostic model was constructed and differential expression of genes in the model was validated by RT-qPCR. Furthermore, a receiver operating characteristic curve and nomogram model were constructed to evaluate the predictive ability of the diagnostic model. Finally, the immune cell types in the merged samples and networks associated with the selected optimal DE-EMGs were constructed. A total of 72 overlapped genes were selected as DE-EMGs, and a five DE-EMG based diagnostic model consisting B4GALT4, ADH4, ACAD11, B4GALT2, and PPP1R3C was established. The areas under the curve of the five genes in the merged training dataset and B4GALT2 in the validation dataset were 0.784 and 0.790, respectively. Moreover, good prognostic prediction ability was observed using the nomogram model (C index = 0.9201; P = 5.507e-14). Significant differences were observed in five immune cell types between the high- and low-BMD groups. These included central memory, effector memory, and activated CD8 T cells, as well as regulatory T cells and activated B cells. A network related to DE-EMGs was constructed, including hsa-miR-23b-3p, DANCR, 17 small-molecule drugs, and two Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways and pyruvate metabolism. Our findings highlighted the important roles of DE-EMGs in the development of osteoporosis. Furthermore, the DANCR/hsa-miR-23b-3p/B4GALT4 axis might provide novel molecular insights into the process of osteoporosis development.
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Resorción Ósea , MicroARNs , Osteoporosis , Humanos , Linfocitos B , Osteoporosis/diagnóstico , Osteoporosis/genética , Metabolismo Energético/genéticaRESUMEN
The contradiction between the activity and stability of metal anodes exists extensively, especially in acid electrooxidation under industrial-level current density. Although the anode modification enhanced the initial activity of anodes, its long-term activity is limited by anode slime accumulation. Herein, a synergistic strategy, coupling the solute environment with the phase control of anodes, is proposed to achieve the trade-off between activity and stability of Pb-based anodes in concentrated sulfuric acid electrolysis. Non-exogenous Mn2+ motivated a series of positive behaviours of reactive-oxygen-species capture, anode reconstruction and corrosion-dependent activity alleviation. The synergistic effects, which are crystal phase-dependent, mainly benefit from the continuous self-healing ability of the specific crystal phase of MnO2 on the anodes by the coexisted Mn2+. Compared with Mn2+/α-MnO2, Mn2+/γ-MnO2 exhibited outperformed activity and stability in boosting oxygen evolution reaction (OER) and reducing hazardous pollutants, which resulted from the energy difference in the rate-determining step of OER and in the selectivity priority of Mn2+/MnO2 oxidation pathway. Interestingly, the pre-coated γ-MnO2 on the anode also presents excellent inheritance, guaranteeing the unchanged crystal phase of MnO2 and the high performance in ultra-low hazardous slime generation in subsequent Mn2+ oxidation. The sustainability of Mn2+/γ-MnO2 was proved in the operating hydrometallurgy conditions on Pb-based anodes. This strategy offers a promising approach for this common issue in electrooxidation-related areas.
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PURPOSE: Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects. METHODS: In this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups. RESULTS: Compared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4+ and CD8+ T cells. CONCLUSION: In conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.
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Citocinas , Progresión de la Enfermedad , Neoplasias de la Boca , Prevotella intermedia , Ubiquitinas , Regulación hacia Arriba , Animales , Ratones , Citocinas/metabolismo , Humanos , Neoplasias de la Boca/patología , Neoplasias de la Boca/microbiología , Ubiquitinas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/microbiología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Infecciones por Bacteroidaceae/microbiología , Línea Celular Tumoral , Ratones Endogámicos BALB C , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/microbiología , Carcinoma de Células Escamosas/tratamiento farmacológico , Antibacterianos/farmacologíaRESUMEN
OBJECTIVE: To provide a comprehensive overview of the current knowledge structure and research hotspots of Cowden syndrome via bibliometrics. METHODS: The articles and reviews related to Cowden syndrome were included from the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace and GraphPad Prism were used to conduct the bibliometric analysis. RESULTS: The number of papers focusing on Cowden syndrome was relatively low initially but increased rapidly from 1997 to 1999, and then maintained small-scale fluctuation. A total of 1,557 papers from 65 countries/regions and 1,762 institutions were identified. The USA was the most productive country, and Ohio State University was the most productive institution. In terms of the number of publications, Human Molecular Genetics ranked first, and Cancer Research was the most frequently cited journal. Eng was the most productive author, and Liaw was the most co-cited author. Phosphatase and tensin homologue (PTEN), germline mutations, gene, cancer, mutations, tumour suppressor gene and breast were high-frequency key words in this field. CONCLUSION: This study was the first comprehensive bibliometric overview of the current state and development of Cowden disease. The mutation of PTEN and associated cancers, especially breast, thyroid and endometrial cancer, could be the focus of future research in this field.
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Neoplasias Endometriales , Síndrome de Hamartoma Múltiple , Humanos , Femenino , Síndrome de Hamartoma Múltiple/genética , Bibliometría , Mama , Bases de Datos FactualesRESUMEN
Purpose: Surgical treatment is the main treatment method for femoral intertrochanteric fractures (FIFs), however, there are lots of implant-related complications after surgery. Our team designed a new intramedullary nail (NIN) to manage such fractures. The purpose of this study was to introduce this new implant and compare it with proximal femoral nail antirotation (PFNA) and InterTAN for treating FIFs. Methods: An AO/OTA 31-A1.3 FIF model was built and three fixation models were created via finite element method, comprising PFNA, InterTAN, and the NIN. Vertical, anteroposterior (A-P) bending, and torsional loads were simulated and applied to the three fixation models. Displacement and stress distribution were monitored. In order to compare PFNA and the NIN deeply, finite element testing was repeated for five times in vertical load case. Results: The finite element analysis (FEA) data indicated that the NIN possessed the most outstanding mechanical properties among the three fixation models. The NIN model had lower maximal stress at implants compared to PFNA and InterTAN models under three load conditions. The trend of maximal stress at bones was similar to that of maximal stress at implants. Besides, the NIN model showed smaller maximal displacement compared with PFNA and InterTAN models under vertical, A-P bending, and torsional load cases. The trend for maximal displacement of fracture surface (MDFS) was almost identical with that of maximal displacement. In addition, there was significant difference between the PFNA and NIN groups in vertical load case (p < 0.05). Conclusion: Compared with PFNA and InterTAN, the NIN displayed the best mechanical properties for managing FIFs, including the lowest von Mises stress at implants and bones, and the smallest maximal displacement and MDFS under vertical, A-P bending, and torsional load cases. Therefore, this study might provide a new choice for patients with FIFs.
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BACKGROUND: Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored. METHODS: P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis. RESULTS: Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment. CONCLUSIONS: Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.
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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.
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Adenocarcinoma , Neoplasias Colorrectales , Humanos , Pronóstico , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Colorrectales/epidemiología , Adenocarcinoma/patologíaRESUMEN
Heavy metal ions (Cr6+, Co2+, Ni2+, and Cu2+) in the electroplating and electrolysis industries are significantly related to process parameters and product quality, even at lower concentrations. Absorption spectroscopy is widely used for substance qualitative and quantitative analysis, which is an analytical method with the potential for real-time monitoring of heavy metal ions concentration in industrial processes. In this paper, a low-concentration heavy metal ion analysis method based on multiple reflection enhanced absorption (MREA) is proposed. Compared with traditional absorption, MREA has the advantages of low concentration detection limit and high-sensitivity. First, a reflective film (Al-SiO2) was prepared and a multiple reflection optical structure was designed to realize multiple parallel reflections of light in the solution medium. Then absorption spectra of low-concentration Cr6+, Co2+, Ni2+ and Cu2+ solutions were measured by MREA and traditional absorption methods. Finally, spectral bandwidth and incident light spots were optimized to obtain a superior absorption enhancement effect. The results showed that MREA could effectively increase the substance absorbance compared with traditional absorption. At the same time, with the optimal spectral bandwidth (0.4 nm) and incident light spot (1 mm), the detection limit of Cr6+, Co2+, Ni2+ and Cu2+ was reduced by 81.48%, 82.52%, 80.92% and 82.93%, respectively. The sensitivity was improved by 5-6 times, which was more obvious for low-concentration detection. In addition, the MREA method can achieve ion concentration analysis when Cr6+, Co2+, Ni2+, and Cu2+ coexist, and the linear correlative coefficients of the C-A curves were all greater than 0.999. Moreover, by adjusting reflectivity of the reflective film and the number of reflections in the optical structure, the results of the MREA method can be further optimized for the low-concentration heavy metal ion analysis. The MREA method has the advantages of simplicity, rapidity and versatility, which can provide the technical foundation for real-time monitoring method development of low-concentration heavy metal ions in industrial processes.
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The current methods for determining high-concentration As(III) in the high-acid matrix from the copper smelting industry are complex, time-consuming, and costly. This limits effective modulation of sulfurizing agent dosage for As(III) removal via sulfurization, aggravating hazardous waste generation. Herein, a simple, rapid, and nondestructive UV high-reference differential absorption spectroscopy was developed to directly determine high-concentration As(III) in simulated high-acid wastewater. Time-dependent density functional theory calculations indicated that the spectral curve redshift with As(III) concentration increasing was related to the decrease of electron transition energies and energy gaps. When using high-reference solutions, the least redshift in the maximum absorption wavelength and the highest upper limit of linear fitting concentration could be obtained. Therefore, the piecewise quantitative linear model of differential absorbance and concentration was established under high-reference. The quantitative range of the model within 0.06-20.00 g/L As(III) with a mean relative error of < 5.0 % and standard recovery rates within 98.0 %-104.0 % indicated high accuracy. Additionally, the relative standard deviations of < 1.5 % (n = 5) revealed good precision. All results indicated the high feasibility of the developed method in alleviating linear deviation caused by redshift and absorption saturation. Furthermore, it has potential significance in saving sulfurizing agent dosage and reducing hazardous waste generation from the source, thereby facilitating a cleaner process for removing As(III) via sulfurization.
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Bacteria use a variety of defense systems to protect themselves from phage infection. In turn, phages have evolved diverse counter-defense measures to overcome host defenses. Here, we use protein structural similarity and gene co-occurrence analyses to screen >66 million viral protein sequences and >330,000 metagenome-assembled genomes for the identification of anti-phage and counter-defense systems. We predict structures for ~300,000 proteins and perform large-scale, pairwise comparison to known anti-CRISPR (Acr) and anti-phage proteins to identify structural homologs that otherwise may not be uncovered using primary sequence search. This way, we identify a Bacteroidota phage Acr protein that inhibits Cas12a, and an Akkermansia muciniphila anti-phage defense protein, termed BxaP. Gene bxaP is found in loci encoding Bacteriophage Exclusion (BREX) and restriction-modification defense systems, but confers immunity independently. Our work highlights the advantage of combining protein structural features and gene co-localization information in studying host-phage interactions.
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Bacteriófagos , Bacteriófagos/metabolismo , Sistemas CRISPR-Cas , Proteínas Virales/genética , Proteínas Virales/metabolismo , Bacterias/genética , Bacteroidetes/metabolismoRESUMEN
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.
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Vacunas contra el Cáncer , Neoplasias Gastrointestinales , Humanos , Vacunas contra el Cáncer/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Inmunoterapia , Resistencia a Medicamentos , Microambiente TumoralRESUMEN
Failure of bone healing after fracture often results in nonunion, but the underlying mechanism of nonunion pathogenesis is poorly understood. Herein, we provide evidence to clarify that the inflammatory microenvironment of atrophic nonunion (AN) mice suppresses the expression levels of DNA methyltransferases 2 (DNMT2) and 3A (DNMT3a), preventing the methylation of CpG islands on the promoters of C-terminal binding protein 1/2 (CtBP1/2) and resulting in their overexpression. Increased CtBP1/2 acts as transcriptional corepressors that, along with histone acetyltransferase p300 and Runt-related transcription factor 2 (Runx2), suppress the expression levels of six genes involved in bone healing: BGLAP (bone gamma-carboxyglutamate protein), ALPL (alkaline phosphatase), SPP1 (secreted phosphoprotein 1), COL1A1 (collagen 1a1), IBSP (integrin binding sialoprotein), and MMP13 (matrix metallopeptidase 13). We also observe a similar phenomenon in osteoblast cells treated with proinflammatory cytokines or treated with a DNMT inhibitor (5-azacytidine). Forced expression of DNMT2/3a or blockage of CtBP1/2 with their inhibitors can reverse the expression levels of BGLAP/ALPL/SPP1/COL1A1/IBSP/MMP13 in the presence of proinflammatory cytokines. Administration of CtBP1/2 inhibitors in fractured mice can prevent the incidence of AN. Thus, we demonstrate that the downregulation of bone healing genes dependent on proinflammatory cytokines/DNMT2/3a/CtBP1/2-p300-Runx2 axis signaling plays a critical role in the pathogenesis of AN. Disruption of this signaling may represent a new therapeutic strategy to prevent AN incidence after bone fracture.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal , Citocinas , ADN (Citosina-5-)-Metiltransferasas , ADN Metiltransferasa 3A , Curación de Fractura , Animales , Ratones , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Citocinas/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metiltransferasas/metabolismo , Osteoblastos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Curación de Fractura/genética , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , ADN Metiltransferasa 3A/genética , ADN Metiltransferasa 3A/metabolismoRESUMEN
Non-communicable diseases (NCDs) are the leading cause of death worldwide. NCDs affect the health status and the quality of life. In addition, continuous NCDs treatment expenses place a heavy economic burden on families and cause huge economic losses to the society. The prevention and treatment of NCDs and reduction of their economic burden are key public health issues. Considering middle-aged and older adult people as the focus, their basic socio-demographic characteristics and health behavior status of this group, and a pooled cross-sections regression model was then used to analyze the main factors affecting the direct economic burden. The results showed that from 2013 to 2018, the prevalence of NCDs among the middle-aged and older adult people in Shaanxi province as well as the direct economic burden of NCDs increased. The effect factors primarily included sex, age, employment status, income level, type of medical insurance, urban or rural residency, level of the health care-providing institutions, visiting times of 2-week, and length of hospital stay. Several measures can be taken to control the onset of NCDs and reduce their direct economic burden.
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Estrés Financiero , Enfermedades no Transmisibles , Persona de Mediana Edad , Humanos , Anciano , Recién Nacido , Enfermedades no Transmisibles/epidemiología , Enfermedades no Transmisibles/terapia , Calidad de Vida , Conductas Relacionadas con la Salud , Estado de SaludRESUMEN
Objective@# To investigate the classification of atrophic glossitis and to study the correlation between the classification and changes of VitB12, folic acid (FOL) and blood cell parameters@*Methods@#A total of 70 patients with atrophic glossitis (AG) were divided into complex type and simple type according to whether they had ulcer or erosion on the tongue mucosa or not. Another 65 healthy subjects during the same period were collected as the control group. The levels of vitamin B12, FOL and blood cell parameters were statistically analyzed using SPSS 25.0 software package.@*Results@#The levels of vitamin B12, red blood cell count (RBC) (3.52 ± 0.69) × 1012·L-1, hemoglobin (HGB)(11.97 ± 1.70) g·dL-1, white blood cell count (WBC) (4.85 ± 1.16) × 109·L-1, neutrophil count (NEUT) (2.76 ± 0.99) × 109·L-1, lymphocyte count (LYMPH) (1.48 ± 0.44) × 109·L-1 in complex type AG group were lower than those in simple type AG group (P<0.05). The levels of mean red blood cell volume (MCV) (104.90 ± 11.13) fL, mean corpuscular hemoglobin (MCH) (34.83 ± 4.56) pg, mean corpuscular hemoglobin concentration (MCHC) (331.09 ± 13.60) g·L-1 were higher than those in the simple type AG group (P<0.05). There was no significant difference in FOL content between these two groups (P>0.05). The levels of VitB12, MCV, MCH, MCHC, WBC, lymph and neut were correlated with the classification of atrophic glossitis (P < 0.05). @*Conclusion@#VitB12 deficiency was more apparent in complex AG, especially in large cell anemia, which correlated with the levels of WBC, NEUT, and LYMPH.
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Objective@# A model was built by neural network analysis to study the relationship between different degrees of vitamin B12 and folic acid deficiency and malnutrition-induced stomatitis.@*Methods@# Data from 30 healthy volunteers and 30 patients with malnutrition-induced stomatitis were collected. The distribution of lesions, the number of affected sites and clinical manifestations were recorded, and the severity was scored. The levels of vitamin B12 and folic acid in the peripheral blood of the two groups were simultaneously measured. The SPSS software was used to analyze the correlation between vitamin B12 and folic acid levels in the peripheral blood of patients with malnutrition-induced stomatitis and healthy volunteers, and the MATLAB software package was used to analyze the data via a neural network.@*Results@#The levels of vitamin B12 and folic acid significantly correlated with the grade of malnutrition-induced stomatitis. Simultaneous B12 and folic acid deficiency linearly correlated with the occurrence and severity of malnutrition-induced stomatitis. Based on this correlation, a thermogram model of malnutrition-induced stomatitis was constructed.@*Conclusion@# Malnutrition-induced stomatitis is closely related to vitamin B12 and folic acid deficiency. Their synergistic effect may promote the occurrence and development of malnutrition-induced stomatitis. The construction of the malnutrition-induced stomatitis model aids the targeted etiological treatment of patients with moderate and severe deficiency to prevent malnutrition-induced stomatitis.
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Objective@#To investigate the clinicopathological features, treatment and prognosis of oralmucosal malignant melanoma to provide a reference for clinical practice.@*Methods@#Data from 19 patients with oralmucosal malignant melanoma were collected, and their clinical manifestations, treatment methods and follow-up results were retrospectively analyzed. @*Results@#Among the 19 patients, 11 cases (58%) had lesions in the gingiva, 7 cases (37%) had lesions in the palate, and 1 case (5%) had lesions in the tongue, the difference was statistically significant (P<0.05). Eight patients had regional lymph node metastasis with a metastasis rate of 42%, of which 4 cases had multiple site metastasis, and the total number of regional lymph node metastasis sites was 15. Among the 19 patients, 3 cases received only surgery, 4 cases received cryotherapy, and 12 cases received combined surgery, cryotherapy and biological immunotherapy. Pathological examination showed malignant melanoma. The positive rates of S-100, HMB-45 and Melan-A were 95%, 89% and 84%, respectively. Kaplan-Meier survival analysis showed that patients with lesions less than 5 cm2 had a higher survival rate (P < 0.05).@*Conclusions@# Oral malignant melanomas usually present as black lesions in the oral mucosa, which are prone to metastasis in early stage. The area of lesions may affect the prognosis of the disease. Therefore, the large range of black lesions or masses should be the alert for the clinicians. Oral malignant melanoma patients are usually treated with combined treatment with surgery, cryotherapy and biological immunotherapy.