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1.
Ying Yong Sheng Tai Xue Bao ; 35(7): 1915-1924, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39233421

RESUMEN

Ecological security pattern is an important spatial way to maintain ecological processes and ensure the stability of ecosystem functions. As the implementation of landscape planning and decision-making, it is critically needed to consider the consistency of differentiated methods and their spatial outputs in the construction of ecological security patterns and the matching and applicability of research objects. From the perspective of integration, we combined the regional topography and landscape characteristics, integrated the morphological spatial pattern analysis and the importance evaluation results of ecosystem services to identify the ecological source, and constructed the ecological security pattern of the Ansai District of Yan'an City, the main implementation area of the Grain-for-Green Project on the Loess Plateau. The results showed that the structural and functional construction methods had low consistency in the identification of spatial protection priority. The integration-oriented method could complement each other and achieve the dual goals of structural connectivity and functional improvement. There were 202 ecological sources in the study area, with a total area of 391.58 km2, accounting for 13.3% of the total area of the study area. There were 110 ecological corridors in the study area, with a total length of 599 km, which were mainly distributed around the river channel, showing a distribution pattern of 'short and narrow dense in the north and south, long and wide in the middle'. The structure-function integration method provides new insights for ecological restoration planning of land space and promotes the research of landscape pattern, process and service.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , China , Conservación de los Recursos Naturales/métodos , Altitud , Ecología/métodos , Planificación Ambiental , Monitoreo del Ambiente/métodos
2.
Front Immunol ; 15: 1432633, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104526

RESUMEN

Mitochondrial damage has a particular impact on the immune system and tumor microenvironment, which can trigger cell stress, an inflammatory response, and disrupt immune cell function, thus all of which can accelerate the progression of the tumor. Therefore, it is of essence to comprehend how the immune system function and the tumor microenvironment interact with mitochondrial dysfunction for cancer treatment. Preserving the integrity of mitochondria or regulating the function of immune cells, such as macrophages, may enhance the efficacy of cancer therapy. Future research should concentrate on the interactions among mitochondria, the immune system, and the tumor microenvironment to identify new therapeutic strategies.


Asunto(s)
Inmunoterapia , Mitocondrias , Neoplasias , Microambiente Tumoral , Humanos , Mitocondrias/metabolismo , Mitocondrias/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Animales
3.
J Mol Med (Berl) ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145815

RESUMEN

Osteoarthritis (OA) is a chronic joint disease with an unclear cause characterized by secondary osteophytes and degenerative changes in the articular cartilage. More than 250 million people are expected to be affected by it by 2050, putting a tremendous socioeconomic strain on the entire world. OA cannot currently be treated with any effective medications that change the illness. Over time, chondrocytes undergo gradual metabolic, structural, and functional changes as a result of aging or abuse. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte homeostasis. By continuously recycling and rebuilding macromolecules or organelles, autophagy functions as a crucial regulatory system to maintain homeostasis during an individual's growth and development. This review uses chondrocytes as its starting point and establishes a strong connection between autophagy and osteoarthritis in order to thoroughly examine the mechanisms behind chondrocyte autophagy in osteoarthritis. Biomarkers of chondrocyte autophagy will be identified, and prospective targeted medications and novel treatment approaches for slowing or preventing the course of OA will be developed based on chondrocyte senescence, autophagy, and apoptosis in OA. KEY MESSAGES: Currently, OA has not been treated with any drugs that can effectively cure it. We hope that by exploring specific targets in the course of osteoarthritis, we can promote the progress of treatment strategies. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte balance. Through the continuous recovery and reconstruction of macromolecules or organelles, autophagy is an important regulatory system for maintaining homeostasis during individual growth and development. In this paper, the close relationship between autophagy and osteoarthritis was established with chondrocytes as the starting point, in order to further explore the mechanism of chondrocyte autophagy in osteoarthritis. The development process of osteoarthritis was studied from the perspective of chondrocytes, and the change of autophagy level had a significant impact on osteoarthritis. Chondrocyte autophagy is mainly determined by intracellular mitochondrial autophagy, so we are committed to finding relevant molecules. Through PI3K/AKT- and MAPK-related pathways, the biomarkers of chondrocyte autophagy were identified, and chondrocyte senescence, autophagy, and apoptosis based on osteoarthritis provided a constructive idea for the development of prospective targeted drugs and new therapies to slow down or prevent the progression of osteoarthritis.

4.
Int J Oncol ; 65(3)2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39054950

RESUMEN

Globally, colorectal cancer (CRC) is the third most common type of cancer. CRC has no apparent symptoms in the early stages of disease, and most patients receive a confirmed diagnosis in the middle or late disease stages. The incidence of CRC continues to increase, and the affected population tends to be younger. Therefore, determining how to achieve an early CRC diagnosis and treatment has become a top priority for prolonging patient survival. Myeloid­derived suppressor cells (MDSCs) are a group of bone marrow­derived immuno­negative regulatory cells that are divided into two subpopulations, polymorphonuclear­MDSCs and monocytic­MDSCs, based on their phenotypic similarities to neutrophils and monocytes, respectively. These cells can inhibit the immune response and promote cancer cell metastasis in the tumour microenvironment (TME). A large aggregation of MDSCs in the TME is often a marker of cancer and a poor prognosis in inflammatory diseases of the intestine (such as colonic adenoma and ulcerative colitis). In the present review, the phenotypic classification of MDSCs in the CRC microenvironment are first discussed. Then, the amplification, role and metastatic mechanism of MDSCs in the CRC TME are described, focusing on genes, gene modifications, proteins and the intestinal microenvironment. Finally, the progress in CRC­targeted therapies that aim to modulate the quantity, function and structure of MDSCs are summarized in the hope of identifying potential screening markers for CRC and improving CRC prognosis and therapeutic options.


Asunto(s)
Neoplasias Colorrectales , Células Supresoras de Origen Mieloide , Microambiente Tumoral , Humanos , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Microambiente Tumoral/inmunología
5.
Medicine (Baltimore) ; 103(25): e38471, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38905423

RESUMEN

Anemia is common in patients with rheumatoid arthritis (RA), and it is unknown whether the dietary inflammatory index (DII) is linked to anemia. This study aimed to clarify the prevalence of anemia in RA patients and its association with the DII. The data utilized in this study were collected from the National Health and Nutrition Examination Survey database from 1999 to 2018. The prevalence of anemia in RA patients was estimated by ethnicity, sex, and age. Weighted multivariate logistic regression was utilized to explore the correlation between anemia risk and DII. The most crucial dietary factors related to the risk of anemia in RA patients were screened by stepwise regression. A nomogram model was established according to key dietary factors. A total of 10.25% (confidence interval, 8.58-11.92%) of RA patients will develop anemia, with the lowest prevalence around the age of 60. In addition, higher DII levels were discovered in anemic patients than in nonanemic patients. In multivariate regression models, an important positive association was revealed between anemia and growing quartiles of DII (Q4 vs Q1: odds ratio = 1.98; confidence interval, 1.25-3.15). In the subgroup analysis, the adjusted relation of DII with anemia in females, Mexicans, smokers, nondrinkers, and age groups ≥ 60 years was statistically significant. The same association was observed in the sensitivity analysis. A nomogram model based on stepwise regression screening of key dietary factors showed good discriminatory power to identify anemic risk in RA patients (area under the curve: 0.707). In patients with RA, high DII levels were associated with the risk of anemia. More attention should be given to controlling dietary inflammation to better prevent and treat anemia.


Asunto(s)
Anemia , Artritis Reumatoide , Dieta , Encuestas Nutricionales , Humanos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Femenino , Masculino , Anemia/epidemiología , Anemia/etiología , Persona de Mediana Edad , Prevalencia , Adulto , Dieta/efectos adversos , Anciano , Factores de Riesgo , Estados Unidos/epidemiología , Inflamación/epidemiología , Estudios Transversales
6.
Heliyon ; 10(9): e30020, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707281

RESUMEN

Background: Gout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed. Methods: For the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database. To obtain the differentially expressed genes (DEGs), we intersected the two data sets. Using the cytohubba algorithm, we identified the key genes and enriched them through GO and KEGG. The gene expression trends of three subgroups (normal control group, intermittent gout group and acute gout attack group) were analyzed by Series Test of Cluster (STC) analysis, and the key genes were screened out, and the diagnostic effect was verified by ROC curve. The expression of key genes in dorsal root nerve and spinal cord of gout mice was analyzed. Finally, the clinical samples of normal control group, hyperuricemia group, intermittent gout group and acute gout attack group were collected, and the expression of key genes at protein level was verified by ELISA. Result: We obtained 59 co-upregulated and 28 co-downregulated genes by comparing the DEGs between gout mouse model data set and human gout data set. 7 hub DEGs(IL1B, IL10, NLRP3, SOCS3, PTGS2) were screened out via Cytohubba algorithm. The results of both GO and KEGG enrichment analyses indicate that 7 hub genes play a significant role in regulating the inflammatory response, cytokine production in immune response, and the TNF signaling pathway. The most representative hub genes SOCS3 and PTGS2 were screened out by Series Test of Cluster, and ROC analysis results showed the AUC values were both up to 1.000. In addition, we found that PTGS2 expression was significantly elevated in the dorsal root ganglia and spinal cord in monosodium urate(MSU)-induced gout mouse model. The ELISA results revealed that the expression of SOCS3 and PTGS2 was notably higher in the acute gout attack and intermittent gout groups compared to the normal control group. This difference was statistically significant, indicating a clear distinction between the groups. Conclusion: Through cross-species comprehensive analysis and experimental verification, SOCS3 and PTGS2 were proved to be new biomarkers for diagnosing gout and predicting disease progression.

7.
J Nanobiotechnology ; 22(1): 298, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38811968

RESUMEN

BACKGROUND: Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, the effectiveness of sorafenib is greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in the cancer's malignant advancement. However, the significance of exosomal circular RNAs in the development of resistance to sorafenib in HCC remains uncertain. METHODS: Ultracentrifugation was utilized to isolate exosomes (Exo-SR) from the sorafenib-resistant HCC cells' culture medium. Transcriptome sequencing and differential expression gene analysis were used to identify the targets of Exo-SR action in HCC cells. To identify the targets of Exo-SR action in HCC cells, transcriptome sequencing and analysis of differential expression genes were employed. To evaluate the impact of exosomal circUPF2 on resistance to sorafenib in HCC, experiments involving gain-of-function and loss-of-function were conducted. RNA pull-down assays and mass spectrometry analysis were performed to identify the RNA-binding proteins interacting with circUPF2. RNA immunoprecipitation (RIP), RNA pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence in situ hybridization (FISH), and rescue assays were used to validate the interactions among circUPF2, IGF2BP2 and SLC7A11. Finally, a tumor xenograft assay was used to examine the biological functions and underlying mechanisms of Exo-SR and circUPF2 in vivo. RESULTS: A novel exosomal circRNA, circUPF2, was identified and revealed to be significantly enriched in Exo-SR. Exosomes with enriched circUPF2 enhanced sorafenib resistance by promoting SLC7A11 expression and suppressing ferroptosis in HCC cells. Mechanistically, circUPF2 acts as a framework to enhance the creation of the circUPF2-IGF2BP2-SLC7A11 ternary complex contributing to the stabilization of SLC7A11 mRNA. Consequently, exosomal circUPF2 promotes SLC7A11 expression and enhances the function of system Xc- in HCC cells, leading to decreased sensitivity to ferroptosis and resistance to sorafenib. CONCLUSIONS: The resistance to sorafenib in HCC is facilitated by the exosomal circUPF2, which promotes the formation of the circUPF2-IGF2BP2-SLC7A11 ternary complex and increases the stability of SLC7A11 mRNA. Focusing on exosomal circUPF2 could potentially be an innovative approach for HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , Resistencia a Antineoplásicos , Exosomas , Ferroptosis , Neoplasias Hepáticas , ARN Circular , Proteínas de Unión al ARN , Sorafenib , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Exosomas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Sorafenib/farmacología , ARN Circular/genética , ARN Circular/metabolismo , Ferroptosis/efectos de los fármacos , Línea Celular Tumoral , Animales , Ratones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Ratones Desnudos , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB C
8.
Int Immunopharmacol ; 132: 112037, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38599100

RESUMEN

Colorectal cancer (CRC) is a typical cancer that accounts for 10% of all new cancer cases annually and nearly 10% of all cancer deaths. Despite significant progress in current classical interventions for CRC, these traditional strategies could be invasive and with numerous adverse effects. The poor prognosis of CRC patients highlights the evident and pressing need for more efficient and targeted treatment. Novel strategies regarding mRNA vaccines for anti-tumor therapy have also been well-developed since the successful application for the prevention of COVID-19. mRNA vaccine technology won the 2023 Nobel Prize in Physiology or Medicine, signaling a new direction in human anti-cancer treatment: mRNA medicine. As a promising new immunotherapy in CRC and other multiple cancer treatments, the mRNA vaccine has higher specificity, better efficacy, and fewer side effects than traditional strategies. The present review outlines the basics of mRNA vaccines and their advantages over other vaccines and informs an available strategy for developing efficient mRNA vaccines for CRC precise treatment. In the future, more exploration of mRNA vaccines for CRC shall be attached, fostering innovation to address existing limitations.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias Colorrectales , Inmunoterapia , Vacunas de ARNm , Animales , Humanos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/inmunología , Inmunoterapia/métodos , Vacunas de ARNm/inmunología , Vacunas de ARNm/uso terapéutico
9.
Int Immunopharmacol ; 131: 111876, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38493688

RESUMEN

Colorectal cancer (CRC) is the third most common cancer and has the second highest mortality rate among cancers. The development of CRC involves both genetic and epigenetic abnormalities, and recent research has focused on exploring the ex-transcriptome, particularly post-transcriptional modifications. RNA-binding proteins (RBPs) are emerging epigenetic regulators that play crucial roles in post-transcriptional events. Dysregulation of RBPs can result in aberrant expression of downstream target genes, thereby affecting the progression of colorectal tumors and the prognosis of patients. Recent studies have shown that RBPs can influence CRC pathogenesis and progression by regulating various components of the tumor microenvironment (TME). Although previous research on RBPs has primarily focused on their direct regulation of colorectal tumor development, their involvement in the remodeling of the TME has not been systematically reported. This review aims to highlight the significant role of RBPs in the intricate interactions within the CRC tumor microenvironment, including tumor immune microenvironment, inflammatory microenvironment, extracellular matrix, tumor vasculature, and CRC cancer stem cells. We also highlight several compounds under investigation for RBP-TME-based treatment of CRC, including small molecule inhibitors such as antisense oligonucleotides (ASOs), siRNAs, agonists, gene manipulation, and tumor vaccines. The insights gained from this review may lead to the development of RBP-based targeted novel therapeutic strategies aimed at modulating the TME, potentially inhibiting the progression and metastasis of CRC.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias Colorrectales , Humanos , Microambiente Tumoral , Proteínas de Unión al ARN/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Matriz Extracelular
10.
Drug Dev Res ; 85(2): e22169, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38477422

RESUMEN

Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil-hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Neutrófilos , Sistemas de Liberación de Medicamentos , Portadores de Fármacos , Nanopartículas/uso terapéutico
12.
Cell Metab ; 36(3): 630-647.e8, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38309268

RESUMEN

Tumors employ diverse strategies for immune evasion. Unraveling the mechanisms by which tumors suppress anti-tumor immunity facilitates the development of immunotherapies. Here, we have identified tumor-secreted fibroblast growth factor 21 (FGF21) as a pivotal immune suppressor. FGF21 is upregulated in multiple types of tumors and promotes tumor progression. Tumor-secreted FGF21 significantly disrupts anti-tumor immunity by rewiring cholesterol metabolism of CD8+T cells. Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. FGF21 knockdown or blockade using a neutralizing antibody normalizes AKT-mTORC1 signaling and reduces excessive cholesterol accumulation in CD8+T cells, thus restoring CD8+T cytotoxic function and robustly suppressing tumor growth. Our findings reveal FGF21 as a "secreted immune checkpoint" that hampers anti-tumor immunity, suggesting that inhibiting FGF21 could be a valuable strategy to enhance the cancer immunotherapy efficacy.


Asunto(s)
Factores de Crecimiento de Fibroblastos , Neoplasias , Proteínas Proto-Oncogénicas c-akt , Humanos , Linfocitos T CD8-positivos , Diana Mecanicista del Complejo 1 de la Rapamicina , Colesterol , Inmunoterapia , Microambiente Tumoral
13.
Int J Oncol ; 64(3)2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38240092

RESUMEN

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.


Asunto(s)
Exosomas , Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Exosomas/metabolismo , Microambiente Tumoral , Neoplasias/patología , ARN/metabolismo , Proteínas/metabolismo , ADN , Lípidos
14.
Ann Surg ; 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38073549

RESUMEN

OBJECTIVE: This study aimed to compare robotic pancreatoduodenectomy (RPD) with laparoscopic pancreatoduodenectomy (LPD) in operative and oncologic outcomes. BACKGROUND: Previous studies comparing RPD with LPD have only been carried out in small, single-center studies with variable quality. METHODS: Consecutive patients from nine centers in China who underwent RPD or LPD between 2015 and 2022 were included. A 1:1 propensity score matching (PSM) was used to minimize bias. RESULTS: Of the 2,255 patients, 1158 underwent RPD and 1097 underwent LPD. Following PSM, 1006 patients were enrolled in each group. The RPD group had significantly shorter operative time (270.0 vs. 305.0 minutes, P<0.001), lower intraoperative blood transfusion rate (5.9% vs. 12.0%, P<0.001), lower conversion rate (3.8% vs. 6.7%, P=0.004), and higher vascular reconstruction rate (7.9% vs. 5.6%, P=0.040) than the LPD group. There were no significant differences in estimated blood loss, postoperative length of stay, perioperative complications, and 90-day mortality. Patients who underwent vascular reconstruction had similar outcomes between the two groups, although they had significantly lower estimated blood loss (300.0 vs. 360.0 mL; P=0.021) in the RPD group. Subgroup analysis on pancreatic ductal adenocarcinoma (PDAC) found no significant differences between the two groups in median recurrence-free survival (14.3 vs. 15.3 mo, P=0.573) and overall survival (24.1 vs. 23.7 mo, P=0.710). CONCLUSIONS: In experienced hands, both RPD and LPD are safe and feasible procedures with similar surgical outcomes. RPD had the perioperative advantage over LPD especially in vascular reconstruction. For PDAC patients, RPD resulted in similar oncological and survival outcomes as LPD.

15.
Heliyon ; 9(12): e22930, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38058438

RESUMEN

Objective: The aim of our study was to investigate whether the Dietary Inflammatory Index (DII) correlated with gout in American adults. Method: The study used data from the 2007-2018 National Health and Nutrition Examination Survey, with 27,710 adults participating. Initially, multivariable analysis was performed, with controls for covariates, to assess the link of DII and gout. Then, restricted cubic splines (RCS) were applied to model the nonlinear relationship of DII and gout. Furthermore, propensity score matching (PSM) as a further study of potential relationships was established. Eventually, subgroup analysis was performed. Result: Participants within the highest DII quartile would be more susceptible to increased risk of gout in the univariate regression model (Q4 vs. Q1, OR = 1.31, CI: 1.05-1.63). Additionally, a positive correlation was detected between gout risk and DII after adjusting on drinking, smoking, gender, race, age, and BMI. Based on RCS analysis, we observed that the risk of gout raised sharply as DII values increased, then flattened, and increased sharply again when the DII was greater than approximately 2.5. After performing the PSM, it was observed that DII correlated in a positive way to the presence of gout on a fully adjusted multivariable model. Subgroup analysis revealed that the link of DII and gout showed no statistical significance in females, blacks, Mexicans, nor in the population that smoked. Conclusion: Greater degrees of pro-inflammation correlate with a higher risk of gout and might be a predisposing factor for gout. Hence, tactics fostering an anti-inflammatory diet for preventing and improving gout in adults should be regarded.

16.
J Inflamm Res ; 16: 4373-4388, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37808954

RESUMEN

Objective: The aim of this study was to investigate the clinical significance of Fibrinogen and Platelet to Pre-albumin Ratio(FPAR) in predicting the prognosis of patients with advanced gastric cancer(AGC) and to construct a predictive model. Methods: We collected clinical data from 489 postoperative patients with AGC. FPAR was divided into high and low groups according to the receiver operating characteristic (ROC) curve. The value of FPAR in predicting the prognosis of progressive gastric cancer was analysed using univariate and multivariable Cox regression analysis and its relationship with clinicopathological features. Finally, the Overall Survival(OS) and recurrence-free survival(RFS) prediction models were constructed and validated using FPAR. Results: Univariate and multifactorial cox regression analysis showed that grade (P<0.001), TNM-stage (P<0.001), chemotherapy (P<0.001), and FPAR (OR=3.054,95% CI:2.088-4.467, P<0.001) were independent risk factors for OS; grade (P=0.021), N-stage (P=0.024), TNM-stage (P=0.033), and FPAR (OR=2.215,95% CI:1.634-3.003, P<0.001) were independent risk factors for RFS. Subgroup analysis showed that the FPAR-low group had higher OS and RFS than the FPAR-high group, regardless of the patient's TNM stage (p<0.05). However, OS was instead higher in the the stage III-FPAR-low group than in the the stage II-FPAR-high group (p<0.05), while RFS was not significantly different. Predictive models incorporating FPAR had better predictive performance than those without FPAR, showing wide range of net benefit and AUC. After correction, the 2-year AUC, 3-year AUC and C-index of the OS model were 0.737, 0.756, and 0.746; the 2-year AUC, 3-year AUC, and C-index of the RFS model were 0.738, 0.758, and 0.711. Conclusion: FPAR levels were associated with prognosis in patients with AGC and could independently predict RFS and OS.

17.
Heliyon ; 9(7): e18242, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37539127

RESUMEN

Background: RNA-binding proteins (RBPs) are closely related to tumors, but little is known about the mechanism of RBPs in tumorigenesis and progression of gastric cancer (GC). As genes do not usually act alone in the pathway deregulation, gene pair combinations are more likely to become stable and accurate biomarkers. The purpose of our research is to establish a novel signature based on RBP gene pairs to predict the prognosis of gastric cancer patients. Methods: We downloaded genetic and clinical information from the TCGA and GEO database. TCGA and GSE13911 were used for screening differentially expressed genes (DEGs). The RBP genes were gathered from previous studies and employed to screen out DE-RBP genes after intersecting with DEGs. Samples were classified according to the relative expression of each pair of DE-RBP genes. The univariate Cox regression analysis and random forest were used to identify hub gene pairs to construct signature for predicting the prognosis of gastric cancer. Time-dependent ROC curves and KM survival curves were performed to evaluate the signature. GSEA was performed in TCGA training cohort and GSE62254 testing cohort to analyze enrichment pathways. Finally, the influence of these gene pairs on the prognosis of GC patients was further elucidated respectively through the combination of high and low expression of the two genes in each hub gene pair. Results: We screened out 6 hub RBP gene pairs (COL5A2/FEN1, POP1/GFRA1, EXO1/PLEKHS1, SLC39A10/CHI3L1, MMP7/PPP1R1 B and SLC5A6/BYSL) to predict the prognosis of patients with gastric cancer. Using the optimal cut-off value to divide patients into high-risk and low-risk groups in the training and testing cohort, we found that the overall survival (OS) of the low-risk group was higher than that of the high-risk group (P < 0.05). The area under the ROC curves for 1, 3, and 5 years were (0.659, 0.744, 0.758) and (0.624, 0.650, 0.653) in two cohorts. Univariate and multivariate Cox regression analysis showed that 6 RBP gene pairs signature were independent prognostic factors for gastric cancer (P < 0.05). In addition, the prognostic survival analysis showed that COL5A2-high/FEN1-low, POP1-low/GFRA1-high, EXO1-low/PLEKHS1-low,SLC39A10-high/CHI3L1-low, MMP7-high/PPP1R1 B-low, SLC5A6-low/BYSL-low had worse OS (P < 0.05). And the gene correlation analysis showed that there was no obvious correlation between the genes in each gene pairs except SLC5A6/BYSL and POP1/GFRA1. Finally, GSEA analysis showed that the high-risk group was enriched in tumor migration, invasion and growth-related pathways. Conclusion: Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.

18.
Int Immunopharmacol ; 121: 110466, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37311355

RESUMEN

Gout is an autoimmune disease characterized by acute or chronic inflammation and damage to bone joints induced due to the precipitation of monosodium urate (MSU) crystals. In recent years, with the continuous development of animal models and ongoing clinical investigations, more immune cells and inflammatory factors have been found to play roles in gouty inflammation. The inflammatory network involved in gout has been discovered, providing a new perspective from which to develop targeted therapy for gouty inflammation. Studies have shown that neutrophil macrophages and T lymphocytes play important roles in the pathogenesis and resolution of gout, and some inflammatory cytokines, such as those in the interleukin-1 (IL-1) family, have been shown to play anti-inflammatory or proinflammatory roles in gouty inflammation, but the mechanisms underlying their roles are unclear. In this review, we explore the roles of inflammatory cytokines, inflammasomes and immune cells in the course of gout development and the research status of therapeutic drugs used for inflammation to provide insights into future targeted therapy for gouty inflammation and the direction of gout pathogenesis research.


Asunto(s)
Artritis Gotosa , Gota , Animales , Ácido Úrico/efectos adversos , Gota/inducido químicamente , Macrófagos , Citocinas/uso terapéutico , Inflamación , Inflamasomas , Artritis Gotosa/inducido químicamente
19.
Front Immunol ; 14: 1149622, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37180158

RESUMEN

CD8+ T cells, a cytotoxic T lymphocyte, are a key component of the tumor immune system, but they enter a hyporeactive T cell state in long-term chronic inflammation, and how to rescue this depleted state is a key direction of research. Current studies on CD8+ T cell exhaustion have found that the mechanisms responsible for their heterogeneity and differential kinetics may be closely related to transcription factors and epigenetic regulation, which may serve as biomarkers and potential immunotherapeutic targets to guide treatment. Although the importance of T cell exhaustion in tumor immunotherapy cannot be overstated, studies have pointed out that gastric cancer tissues have a better anti-tumor T cell composition compared to other cancer tissues, which may indicate that gastrointestinal cancers have more promising prospects for the development of precision-targeted immunotherapy. Therefore, the present study will focus on the mechanisms involved in the development of CD8+ T cell exhaustion, and then review the landscapes and mechanisms of T cell exhaustion in gastrointestinal cancer as well as clinical applications, which will provide a clear vision for the development of future immunotherapies.


Asunto(s)
Neoplasias Gastrointestinales , Neoplasias Gástricas , Humanos , Linfocitos T CD8-positivos , Epigénesis Genética , Agotamiento de Células T , Neoplasias Gastrointestinales/terapia , Anticuerpos
20.
Cell Death Dis ; 14(5): 299, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37130837

RESUMEN

In response to stress, cells make a critical decision to arrest or undergo apoptosis, mediated in large part by the tumor suppressor p53. Yet the mechanisms of these cell fate decisions remain largely unknown, particularly in normal cells. Here, we define an incoherent feed-forward loop in non-transformed human squamous epithelial cells involving p53 and the zinc-finger transcription factor KLF5 that dictates responses to differing levels of cellular stress from UV irradiation or oxidative stress. In normal unstressed human squamous epithelial cells, KLF5 complexes with SIN3A and HDAC2 repress TP53, allowing cells to proliferate. With moderate stress, this complex is disrupted, and TP53 is induced; KLF5 then acts as a molecular switch for p53 function by transactivating AKT1 and AKT3, which direct cells toward survival. By contrast, severe stress results in KLF5 loss, such that AKT1 and AKT3 are not induced, and cells preferentially undergo apoptosis. Thus, in human squamous epithelial cells, KLF5 gates the response to UV or oxidative stress to determine the p53 output of growth arrest or apoptosis.


Asunto(s)
Células Epiteliales , Factores de Transcripción de Tipo Kruppel , Proteína p53 Supresora de Tumor , Humanos , Apoptosis/genética , Diferenciación Celular , Factores de Transcripción de Tipo Kruppel/genética , Estrés Oxidativo , Proteína p53 Supresora de Tumor/genética
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