RESUMO
Purpose: Hashimoto's thyroiditis (HT) is a significant public health concern, particularly among females. While existing studies have explored the correlation between serum iron levels and HT, limited research has specifically focused on this association in reproductive-age females. Our study aims to investigate the relationship between serum iron and HT. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) database (2007-2012), we employed weighted multivariate logistic regression models, an XGBoost model, and smooth curve fitting. We assessed the correlation between serum iron and HT and examined linear and non-linear relationships with thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). Results: Among 2,356 participants, each unit increase in serum iron was associated with a 43% reduced risk of HT (Odds Ratios (OR) 0.574; 95% Confidence Interval (CI) 0.572, 0.576). Quartile analysis confirmed these effects. The XGBoost model identified serum iron as the most significant variable correlated with HT. Smooth curves revealed a linear association between log2-transformed serum iron and HT. Additionally, log2-transformed serum iron inversely correlated with TPOAb levels (ß -15.47; 95% CI -25.01, -5.92), while a non-linear relationship was observed with TgAb. Conclusion: Our study reveals that in reproductive-age women, every unit increase in serum iron is associated with a 43% lower risk of HT, demonstrating an inverse relationship. Additionally, serum iron exhibits a negative correlation with TPOAb and a non-linear association with TgAb.
RESUMO
Background: Breast cancer, particularly triple-negative (TNBC), is a leading malignancy with aggressive traits and high metastasis rates. Clinical trial is an important tool for optimizing therapeutic strategies in the evaluation of the safety and efficacy for TNBC. Our bibliometric study of TNBC clinical trials aims to assess therapeutic strategies, identify trends, and explore advancements in treatment. We focus on mapping knowledge development, including key research entities and topics, and analyzing research trends and emerging methods. This analysis intends to inform future research, especially in personalized and precision medicine for TNBC. Methods: We selected publications on clinical trials for the treatment of TNBC from 1997 to 2024 in the Web of Science Core Collection (WoSCC). After an initial screening, we downloaded key data including titles, publication years, authors, countries, institutional affiliations, journals, keywords, and abstracts, and saved them in BibTex format. We then conducted a bibliometric analysis using Bibliometrix in R and VOSviewer to illustrate the prospects, highlights, and trends of TNBC treatment options. Furthermore, to emphasize the hot topics in TNBC treatment strategies, we performed a bibliometric analysis of immunotherapy using the same approach. Results: 1907 publications were included, most of which were from China, Italy, and the United States. The number of annual publications has increased dramatically since 2010. The focus of TNBC clinical trial research has shifted from understanding the biology, such as breast cancer subtyping and genotyping, to novel therapeutic approaches. The major advancement in clinical trials is the switch from late-stage palliative treatment to early preoperative neoadjuvant therapy, as more TNBC cases are discovered at an early stage. Immunotherapy is also highlighted with additional alternatives for advanced or metastasized TNBC, such as targeted inhibitors with unusual mutation rates and antibody drug conjugates (ADC). Conclusions: This investigation made it apparent how immunotherapy has recently made major advancements in TNBC treatment plans and how ADCs, or targeted therapies, are currently popular for TNBC. By identifying significant papers, comprehending trending topics, and collaborating across multiple disciplines, this study may accelerate research on TNBC therapy options.
RESUMO
Establishing predictive models for the pathological response and lymph node metastasis in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) based on MRI radiomic features derived from the tumor and mesorectal compartment (MC). This study included 209 patients with LARC who underwent rectal MRI both before and after nCRT. The patients were divided into a training set (n = 146) and a test set (n = 63). Regions of interest (ROIs) for the tumor and MC were delineated on both pre- and post-nCRT MRI images. Radiomic features were extracted, and delta radiomic features were computed. The predictive endpoints were pathological complete response (pCR), pathological good response (pGR), and lymph node metastasis (LNM). Feature selection for various models involved sequentially removing features with a correlation coefficient > 0.9, and features with P-values ≥ 0.05 in univariate analysis, followed by LASSO regression on the remaining features. Logistic regression models were developed, and their performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among the 209 LARC patients, the number of patients achieving pCR, pGR, and LNM were 44, 118, and 40, respectively. The optimal model for predicting each endpoint is the combined model that incorporates pre- and delta-radiomics features for both the tumor and MC. These models exhibited superior performance with AUC values of 0.874 (for pCR), 0.801 (for pGR), and 0.826 (for LNM), outperforming the MRI tumor regression grade (mrTRG) which yielded AUC values of 0.800, 0.715, and 0.603, respectively. The results demonstrate the potential utility of the tumor and MC radiomics features, in predicting treatment efficacy among LARC patients undergoing nCRT.
Assuntos
Metástase Linfática , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Metástase Linfática/diagnóstico por imagem , Idoso , Adulto , Resultado do Tratamento , Curva ROC , Quimiorradioterapia/métodos , RadiômicaRESUMO
Introduction: Enterocytozoon bieneusi is one of the most important zoonotic pathogens, responsible for nearly 90% of human infections. Its host spectrum is broad in China, encompassing humans, non-human primates, domestic animals, wildlife, and wastewater. Wild rodents have the potential to act as carriers of E. bieneusi, facilitating the parasite's transmission to humans and domestic animals. Methods: The present study involved the collection of 344 wild rodents, representing nine species, from three provinces in China. The prevalence and genotypes of E. bieneusi were determined through amplification of the ITS gene. Evolutionary analysis was conducted using Mega 5.0 with the neighbor-joining method (Kimura 2-parameter model, 1,000 replicates). Results: Among the sampled wild rodents, 41 (11.92%) were tested positive for E. bieneusi. Rattus flavipectus exhibited the highest prevalence (11/39), while Bandicota indica and Rattus rattus sladeni showed no infections (0/39 and 0/5, respectively), highlighting significant differences. Environmental factors strongly influenced E. bieneusi infection; rodents residing in lake beaches (10.27%, 15/146) and fields (19.95%, 18/95) were more susceptible compared to those in mountainous areas (7.77%, 8/103). The study identified four known genotypes (D, Type IV, SDD5, PigEBITS7) and five novel genotypes (HNRV-1 to HNRV-3, GXRL-1, GXRL-2) in the investigated wild rodents, with Genotype D exhibiting the highest prevalence. Discussion: Remarkably, this study reports the presence of E. bieneusi, R. flavipectus, M. fortis, A. agrarius, R. losea, and N. lotipes for the first time. These findings underscore the common occurrence of E. bieneusi infection in wild rodents in China, highlighting its diverse nature and significant potential for zoonotic transmission. Hence, it is imperative to conduct a comprehensive epidemiological investigation of rodent infection with E. bieneusi, particularly focusing on wild rodents that are closely associated with humans. Additionally, developing appropriate measures and monitoring strategies to minimize the risk of infection is essential.
RESUMO
Blastocystis is a common intestinal protist in humans and animals. Currently, Blastocystis infection in bar-headed geese is unknown. To understand the prevalence and distribution of Blastocystis subtypes in bar-headed geese, fecal samples were collected from 358 bar-headed geese in three regions. The total infection rate of Blastocystis in bar-headed in China was 5.9% (21/358), with 5.0% (6/120) in Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, Sichuan province, 11.8% (14/119) in Maqu county, Gansu province, and 0.8% (1/119) in Caohai, Wei ning county, Guizhou province. The differences in prevalence rates by region were statistically significant. Sequences analyses showed that one known subtype (ST7, n = 16) and one potentially novel ST (n = 5) in bar-headed geese were detected in this study. This is the first report on the prevalence and subtype distribution of Blastocystis in bar-headed geese, which will improve our understanding of the epidemiology and public health implications of Blastocystis infection in wild migratory birds.
Assuntos
Infecções por Blastocystis , Blastocystis , Fezes , Gansos , Animais , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/veterinária , Infecções por Blastocystis/parasitologia , Gansos/parasitologia , Blastocystis/isolamento & purificação , Blastocystis/classificação , China/epidemiologia , Prevalência , Fezes/parasitologia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/parasitologia , FilogeniaRESUMO
BACKGROUND: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. OBJECTIVE: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. METHODS: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. RESULTS: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 µM, 47 µM, 46.5 µM and 9.8 µM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. CONCLUSION: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.
RESUMO
BACKGROUND: Accurate prognostic assessment is vital for the personalized treatment of endometrial cancer (EC). Although radiomics models have demonstrated prognostic potential in EC, the impact of region of interest (ROI) delineation strategies and the clinical significance of peritumoral features remain uncertain. Our study thereby aimed to explore the predictive performance of varying radiomics models for the prediction of LVSI, DMI, and disease stage in EC. METHODS: Patients with 174 histopathology-confirmed EC were retrospectively reviewed. ROIs were manually delineated using the 2D and 3D approach on T2-weighted MRI images. Six radiomics models involving intratumoral (2Dintra and 3Dintra), peritumoral (2Dperi and 3Dperi), and combined models (2Dintra + peri and 3Dintra + peri) were developed. Models were constructed using the logistic regression method with five-fold cross-validation. Area under the receiver operating characteristic curve (AUC) was assessed, and was compared using the Delong's test. RESULTS: No significant differences in AUC were observed between the 2Dintra and 3Dintra models, or the 2Dperi and 3Dperi models in all prediction tasks (P > 0.05). Significant difference was observed between the 3Dintra and 3Dperi models for LVSI (0.738 vs. 0.805) and DMI prediction (0.719 vs. 0.804). The 3Dintra + peri models demonstrated significantly better predictive performance in all 3 prediction tasks compared to the 3Dintra model in both the training and validation cohorts (P < 0.05). CONCLUSIONS: Comparable predictive performance was observed between the 2D and 3D models. Combined models significantly improved predictive performance, especially with 3D delineation, suggesting that intra- and peritumoral features can provide complementary information for comprehensive prognostication of EC.
Assuntos
Neoplasias do Endométrio , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Humanos , Feminino , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Imageamento Tridimensional/métodos , Estudos Retrospectivos , Projetos Piloto , Prognóstico , Idoso , Adulto , Idoso de 80 Anos ou mais , Curva ROC , RadiômicaRESUMO
Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains poorly understood. Here, we demonstrate the involvement of ß-hexosaminidase B (HEXB) in mediating EV release in response to oxidative stress, thereby promoting the development of hepatocellular carcinoma (HCC). Mechanistically, reactive oxygen species (ROS) stimulate the nuclear translocation of transcription factor EB (TFEB), leading to the upregulation of both HEXB and its antisense lncRNA HEXB-AS. HEXB-AS can bind HEXB to form a protein/RNA complex, which elevates the protein stability of HEXB. The stabilized HEXB interacts with lysosome-associated membrane glycoprotein 1 (LAMP1), disrupting lysosome-multivesicular body (MVB) fusion, which protects EVs from degradation. Knockdown of HEXB efficiently inhibits EV release and curbs HCC growth both in vitro and in vivo. Moreover, targeting HEXB by M-31850 significantly inhibits HCC growth, especially when combined with GW4869, an inhibitor of exosome release. Our results underscore the critical role of HEXB as a modulator that promotes EV release during HCC development.
Assuntos
Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Estresse Oxidativo , Vesículas Extracelulares/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Animais , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Regulação para Cima , Linhagem Celular Tumoral , Proliferação de Células , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/genética , Espécies Reativas de Oxigênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Masculino , Camundongos NusAssuntos
Vírus da Cinomose Canina , Cinomose , Genoma Viral , Filogenia , Sus scrofa , Animais , Vírus da Cinomose Canina/genética , Vírus da Cinomose Canina/isolamento & purificação , Vírus da Cinomose Canina/classificação , Sus scrofa/virologia , Cinomose/virologia , Suínos , Sequenciamento Completo do Genoma , RNA Viral/genética , Análise de Sequência de DNARESUMO
Cryptosporidium spp. is an important foodborne and waterborne pathogen in humans and animals, causing diarrhoea in humans and respiratory and gastrointestinal diseases in birds. However, reports of Cryptosporidium infection in bar-headed goose are limited. To determine the infection rate and species/genotypes of Cryptosporidium in bar-headed goose in China, a total of 358 fecal samples were collected from 3 regions. Nested PCR was used to amplify Cryptosporidium SSU rRNA regions from the fecal extracted-DNA samples. The total infection rate of Cryptosporidium in bar-headed in China was 3.9 % (14/358), with 4.2 % (5/120) in Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, Sichuan province, 7.6 % (9/119) in Maqu county, Gansu province, and 0.0 % (0/119) in Caohai, Wei ning county, Guizhou province. The differences in prevalence rate by region were statistically significant. All positive samples were identified as Cryptosporidium goose genotype I (n = 14). This is the first systematic investigation of the epidemiological status and dominant species/genotypes of Cryptosporidium in bar-headed goose in China, thereby enhancing our understanding of the epidemiology of Cryptosporidium infection in wild migratory birds.
Assuntos
Criptosporidiose , Cryptosporidium , Fezes , Gansos , Genótipo , Animais , Cryptosporidium/genética , Cryptosporidium/isolamento & purificação , Cryptosporidium/classificação , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , China/epidemiologia , Prevalência , Gansos/parasitologia , Fezes/parasitologia , Reação em Cadeia da Polimerase/veterinária , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/parasitologia , DNA de Protozoário/análiseRESUMO
Blastocystis is a protist that is distributed in the gut tract of humans and animals. However, the reports about Blastocystis infection in Tibetan antelope are scarce. We collected 173 Tibetan antelope feces samples from Xinjiang, Qinghai and Xizang, and amplified the SSU rRNA gene of 600 bp region of Blastocystis in our research. Fifty-one samples in total were positive for Blastocystis, with all subtypes being ST31. The lowest prevalence of Blastocystis was observed in Xizang (2/20, 9.1%), followed by Qinghai (18/92, 16.4%), Xinjiang (31/61, 33.7%). The highest prevalence of Blastocystis in Tibetan antelope was detected during the summer was (19/30, 38.8%). This is the first research work regarding the Blastocystis subtypes ST31 in Tibetan antelope. Our research provides information for future researches on the distribution of this Blastocystis subtype and the control of Blastocystis infection.
Assuntos
Antílopes , Infecções por Blastocystis , Blastocystis , Humanos , Animais , Blastocystis/genética , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/veterinária , Tibet/epidemiologia , Antílopes/genética , Fezes , Filogenia , Prevalência , Variação GenéticaRESUMO
A systematic review and meta-analysis were performed to identify the global prevalence and factors associated with Toxoplasma gondii infection in wild birds. Six bibliographic databases (Chinese National Knowledge Infrastructure, VIP Chinese Journal Database, Wanfang Data, PubMed, Web of science and ScienceDirect) were searched from inception to February 2023. The search yielded 1220 records of which 659 articles underwent full-text evaluation, which identified 49 eligible articles and 16,030 wild bird samples that were included in the meta-analysis. The estimated pooled global prevalence of T. gondii infection in wild birds was 16.6%. Out of the variables tested, publication year after 2020 and climate type were significantly associated with T. gondii infection (P<0.01). Our data indicate that the prevalence of T. gondii in wild birds can be influenced by epidemiological variables. Further research is needed to identify the biological, environmental, anthropogenic, and geographical risk factors which impact the ecology and prevalence of T. gondii in wild birds.
Assuntos
Toxoplasma , Toxoplasmose Animal , Animais , Prevalência , Toxoplasmose Animal/epidemiologia , Animais Selvagens , Fatores de Risco , Aves , Estudos SoroepidemiológicosRESUMO
OBJECTIVES: Diagnostic imaging plays an important role in the pre-treatment workup of knee osteoarthritis (OA) and rheumatoid arthritis (RA). Herein, we identified a useful MRI sign of infrapatellar fat pad (IPFP) to improve diagnosis. METHODS: Eighty-one age- and sex-matched RA and OA patients each, with pathological diagnosis and pre-treatment MRI were retrospectively evaluated. All randomized MR images were blinded and independently reviewed by two radiologists. The assessment process included initial diagnosis, sign evaluation, and final diagnosis, with a 3-week interval between each assessment. Broken-fat pad (BFP) sign was assessed on sagittal T2-weighted-imaging in routine MRI. The area under the curve and Cohen's kappa (κ) were used to assess the classification performance. Two shape features were extracted from IPFP for quantitative interpretation. RESULTS: The median age of the study population was 57.6 years (range: 31.0-78.0 years). The BFP sign was detected more frequently in patients with RA (72.8%) than those with OA (21.0%). Both radiologists achieved better performance by referring to the BFP sign, with accuracies increasing from 58.0 to 75.9% and 72.8 to 79.6%, respectively. The inter-reader correlation coefficient showed an increase from fair (κ = 0.30) to substantial (κ = 0.75) upon the consideration of the BFP sign. For quantitative analysis, the IPFP of RA had significantly lower sphericity (0.54 ± 0.04 vs. 0.59 ± 0.03, p < 0.01). Despite larger surface-volume-ratio of RA (0.38 ± 0.05 vs. 0.37 ± 0.04, p = 0.25) than that of OA, there was no statistical difference. CONCLUSIONS: The BFP sign is a potentially important diagnostic clue for differentiating RA from OA with routine MRI and reducing misdiagnosis. CRITICAL RELEVANCE STATEMENT: With the simple and feasible broken-fat pad sign, clinicians can help more patients with early accurate diagnosis and proper treatment, which may be a valuable addition to the diagnostic workup of knee MRI assessment. KEY POINTS: ⢠Detailed identification of infrapatellar fat pad alterations of patients may be currently ignored in routine evaluation. ⢠Broken-fat pad sign is helpful for differentiating rheumatoid arthritis and osteoarthritis. ⢠The quantitative shape features of the infrapatellar fat pad may provide a possible explanation of the signs. ⢠This sign has good inter-reader agreements and is feasible for clinical application.
RESUMO
BACKGROUND AND AIMS: Protein tyrosine sulfation (PTS) is a common posttranslational modification that regulates a variety of physiological and pathological processes. However, the role of PTS in cancer remains poorly understood. The goal of this study was to determine whether and how PTS plays a role in HCC progression. APPROACH AND RESULTS: By mass spectrometry and bioinformatics analysis, we identified SAV1 as a novel substrate of PTS in HCC. Oxidative stress upregulates the transcription of SLC35B2, a Golgi-resident transporter of sulfate donor 3'-phosphoadenosine 5'-phosphosulfate, leading to increased sulfation of SAV1. Sulfation of SAV1 disrupts the formation of the SAV1-MST1 complex, resulting in a decrease of MST1 phosphorylation and subsequent inactivation of Hippo signaling. These molecular events ultimately foster the growth of HCC cells both in vivo and in vitro. Moreover, SLC35B2 is a novel transcription target gene of the Hippo pathway, constituting a positive feedback loop that facilitates HCC progression under oxidative stress. CONCLUSIONS: Our findings reveal a regulatory mechanism of the SLC35B2/SAV1 sulfation axis in response to oxidative stress, highlighting its potential as a promising therapeutic target for HCC.
RESUMO
Loss of E-cadherin (ECAD) is required in tumor metastasis. Protein degradation of ECAD in response to oxidative stress is found in metastasis of hepatocellular carcinoma (HCC) and is independent of transcriptional repression as usually known. Mechanistically, protein kinase A (PKA) senses oxidative stress by redox modification in its ß catalytic subunit (PRKACB) at Cys200 and Cys344. The activation of PKA kinase activity subsequently induces RNF25 phosphorylation at Ser450 to initiate RNF25-catalyzed degradation of ECAD. Functionally, RNF25 repression induces ECAD protein expression and inhibits HCC metastasis in vitro and in vivo. Altogether, these results indicate that RNF25 is a critical regulator of ECAD protein turnover, and PKA is a necessary redox sensor to enable this process. This study provides some mechanistic insight into how oxidative stress-induced ECAD degradation promotes tumor metastasis of HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Estresse Oxidativo , Humanos , Caderinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Proteólise , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BRAF V600E attracts wide attention in the treatment of colorectal cancer (CRC) as stratifying and predicting a refractory classification of CRC. Recent evidence indicates that Wnt/ß-catenin signaling is broadly activated and participates in the refractoriness of BRAF V600E CRC, but the underlying molecular mechanism needs to be elucidated. Here, heat shock 70 kDa protein 8 (HSPA8), an essential regulator in chaperone-mediated autophagy (CMA), is identified as a potential therapeutic target for advanced BRAF V600E CRC. These results show that HSPA8 is transcriptionally upregulated in BRAF V600E CRC, which promotes CMA-dependent degradation of caveolin-1 (CAV1) to release ß-catenin into the nucleus and thus activates the Wnt/ß-catenin pathway, contributing to metastasis and progression of BRAF V600E CRC. Of note, HSPA8 directly interacts with the KIFSN motif on CAV1, the interaction can be enhanced by p38 MAPK-mediated CAV1 S168 phosphorylation. Furthermore, pharmacological targeting HSPA8 by VER155008 exhibits synergistic effects with BRAF inhibitors on CRC mouse models. In summary, these findings discover the important role of the HSPA8/CAV1/ß-catenin axis in the development of refractory BRAF V600E CRC and highlight HSPA8 as a predictive biomarker and therapeutic target in clinical practice.
Assuntos
Autofagia Mediada por Chaperonas , Neoplasias Colorretais , Animais , Camundongos , beta Catenina/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Caveolina 1/uso terapêutico , Neoplasias Colorretais/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas B-raf/uso terapêuticoRESUMO
Cyanide extraction dominates the gold smelting industry, which leads to the generation of large amounts of cyanide-containing wastewater. In this study, Aneurinibacillus tyrosinisolvens strain named JK-1 was used for cyanide wastewater biodegradation. First, we tested the performance of JK-1 in degrading cyanide under different conditions. Then, we screened metabolic compounds and pathways associated with cyanide degradation by JK-1. Finally, we explored the potential JK-1-mediated cyanide degradation pathway. Our results showed that the optimal pH and temperature for cyanide biodegradation were 7.0 and 30 °C, respectively; under these conditions, a degradation rate of >98% was achieved within 48 h. Untargeted metabolomics results showed that increased cyanide concentration decreased the abundance of metabolic compounds by 71.1% but upregulated 32 metabolic pathways. The Kyoto Encyclopedia of Genes and Genomes enrichment results revealed significant changes in amino acid metabolism pathways during cyanide degradation by JK-1, including cyanoamino acid metabolism, ß-alanine metabolism, and glutamate metabolism. Differential metabolic compounds included acetyl-CoA, l-asparagine, l-glutamic acid, l-phenylalanine, and l-glutamine. These results confirmed that cyanide degradation by JK-1 occurs through amino acid assimilation. This study provides new insights into the mechanism of cyanide biodegradation, which can be applied in the treatment of cyanide wastewater or tailings.
Assuntos
Cianetos , Águas Residuárias , Cianetos/análise , Biodegradação Ambiental , Reatores Biológicos , AminoácidosRESUMO
OBJECTIVE: This study aimed to extract radiomics features from MRI using machine learning (ML) algorithms and integrate them with clinical features to build response prediction models for patients with spinal metastases undergoing stereotactic body radiotherapy (SBRT). METHODS: Patients with spinal metastases who were treated using SBRT at our hospital between July 2018 and April 2023 were recruited. We assessed their response to treatment using the revised Response Evaluation Criteria in Solid Tumors (version 1.1). The lesions were categorized into progressive disease (PD) and non-PD groups. Radiomics features were extracted from T1-weighted image (T1WI), T2-weighted image (T2WI), and fat-suppression T2WI sequences. Feature selection involved intraclass correlation coefficients, minimal-redundancy-maximal-relevance, and least absolute shrinkage and selection operator methods. Thirteen ML algorithms were employed to construct the radiomics prediction models. Clinical, conventional imaging, and radiomics features were integrated to develop combined models. Model performance was evaluated using receiver operating characteristic (ROC) curve analysis, and the clinical value was assessed using decision curve analysis. RESULTS: We included 194 patients with 142 (73.2%) lesions in the non-PD group and 52 (26.8%) in the PD group. Each region of interest generated 2264 features. The clinical model exhibited a moderate predictive value (area under the ROC curve, AUC = 0.733), while the radiomics models demonstrated better performance (AUC = 0.745-0.825). The combined model achieved the best performance (AUC = 0.828). CONCLUSION: The MRI-based radiomics models exhibited valuable predictive capability for treatment outcomes in patients with spinal metastases undergoing SBRT. CRITICAL RELEVANCE STATEMENT: Radiomics prediction models have the potential to contribute to clinical decision-making and improve the prognosis of patients with spinal metastases undergoing SBRT. KEY POINTS: ⢠Stereotactic body radiotherapy effectively delivers high doses of radiation to treat spinal metastases. ⢠Accurate prediction of treatment outcomes has crucial clinical significance. ⢠MRI-based radiomics models demonstrated good performance to predict treatment outcomes.
RESUMO
BACKGROUND: The extracellular matrix (ECM), a fundamental constituent of all tissues and organs, is crucial for shaping the tumor microenvironment. Dysregulation of ECM remodeling has been closely linked to tumor initiation and progression, where specific signaling pathways, including redox signaling, play essential roles. Reactive oxygen species (ROS) are risk factors for carcinogenesis whose excess can facilitate the oxidative damage of biomacromolecules, such as DNA and proteins. Emerging evidence suggests that redox effects can aid the modification, stimulation, and degradation of ECM, thus affecting ECM remodeling. These alterations in both the density and components of the ECM subsequently act as critical drivers for tumorigenesis. In this review, we provide an overview of the functions and primary traits of the ECM, and it delves into our current understanding of how redox reactions participate in ECM remodeling during cancer progression. We also discuss the opportunities and challenges presented by clinical strategies targeting redox-controlled ECM remodeling to overcome cancer. CONCLUSIONS: The redox-mediated ECM remodeling contributes importantly to tumor survival, progression, metastasis, and poor prognosis. A comprehensive investigation of the concrete mechanism of redox-mediated tumor ECM remodeling and the combination usage of redox-targeted drugs with existing treatment means may reveal new therapeutic strategy for future antitumor therapies.
RESUMO
Four species of porcine circoviruses (PCV1-4) have been reported to circulate in Chinese domestic pigs, while the epizootiology of these viruses in free-ranging wild boars in China remains unknown. In this study, tissue and serum samples collected from diseased or apparently healthy wild boars between 2018 and 2020 in 19 regions of China were tested for the prevalence of PCV1-4 infections. Positive rates of PCV1, PCV2, and PCV3 DNA in the tissue samples of Chinese wild boars were 1.6% (4/247), 58.3% (144/247), and 10.9% (27/247) respectively, with none positive for PCV4. Sequence analysis of viral genome showed that the four PCV1 strains distributed in Hunan and Inner Mongolia shared 97.5%-99.6% sequence identity with global distributed reference strains. Comparison of the ORF2 gene sequences showed that 80 PCV2 strains widely distributed in 18 regions shared 79.5%-100% sequence identity with reference strains from domestic pigs and wild boars, and were grouped into PCV2a (7), PCV2b (31) and PCV2d (42). For PCV3, 17 sequenced strains shared 97.2%-100% nucleotide identity at the genomic level and could be divided into PCV3a (3), PCV3b (2) and PCV3c (12) based on the phylogeny of ORF2 gene sequences. Serological data revealed antibody positive rates against PCV1 and PCV2 of 11.4% (19/167) and 53.9% (90/167) respectively. The data obtained in this study improved our understanding about the epidemiological situations of PCVs infection in free-ranging wild boars in China and will be valuable for the prevention and control of diseases caused by PCVs infection.