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BACKGROUND: Platelet contains growth factors that enhance tissue repair mechanisms, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF-AA and -AB), and transforming growth factor (TGF)-ß. Autologous platelet-rich plasma (PRP) has been shown to significantly improve the treatment of tendon injuries compared with hyaluronic acid and placebo. The topic of agreement between platelet concentrations and growth factors has been covered in some previous studies, but growth factor levels did not correlate well with platelet concentrations. METHOD: In this study, autologous PRP was prepared by concentrating platelets through a J6-MI centrifuge. The automatic hematology analyzer Sysmex XN-20 was used to analyze the platelet concentration in PRP, and the PRP growth factors were determined by ELISA, including PDGF, transforming growth factor- ß1 (TGF-ß1), and EGF. Statistical analysis was conducted on data from 107 patients who received autologous PRP using Pearson correlation analysis. RESULTS: Pearson correlation analysis revealed PDGF, TGF, and EGF had a strong positive correlation with the platelet concentration of the final PRP product (r = 0.697, p < 0.0001; r = 0.488, p < 0.0001; r = 0.572, p < 0.0001, respectively) CONCLUSIONS: There was a strong positive correlation between the concentration of platelets in the final PRP product and the levels of PDGF-AB, TGF-ß, and EGF. These results suggested straightforward and cost-effective growth factor tests can provide valuable information about platelet content in PRP.
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Péptidos y Proteínas de Señalización Intercelular , Plasma Rico en Plaquetas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Péptidos y Proteínas de Señalización Intercelular/sangre , Recuento de Plaquetas , Plasma Rico en Plaquetas/metabolismo , Plasma Rico en Plaquetas/químicaRESUMEN
We propose that a transition from positive optical torque (OT) to negative OT occurs in a dipolar nanoparticle subjected to a simple optical field composed of two circularly polarized plane waves. This phenomenon can be observed in a phase-change nanoparticle comprising insulating and metallic phases. The analytical expression based on the multipole expansion theory reveals that the positive OT in the metallic phase originates from the electric response during light-matter interaction. However, in the insulating phase, the magnetic response is excited, leading to a significant negative OT due to the contribution of the magnetic field-magnetic dipole interaction. It is noted that the phenomenon of reversible transverse OT is robust to the angle between two constituent plane waves, ensuring its practical application.
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Macrophage-based cell therapeutics is an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfilling their therapeutic potential. Here, we establish a robust macrophage-manufacturing platform (Mo-Mac) and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA. Using single-cell transcriptomic analysis as an unbiased approach, we found that >90% cells in the final product were macrophages while the rest primarily comprised T cells, B cells, natural killer cells, promyelocytes, promonocytes, and hematopoietic stem cells. This analysis also guided the development of flow-cytometry strategies to assess cell compositions in the manufactured product to meet requirements by the National Medical Products Administration. To modulate macrophage functionality, as an illustrative example we examined whether the engulfment capability of macrophages could be enhanced by mRNA technology. We found that efferocytosis was increased in vitro when macrophages were electroporated with m1Ψ-modified mRNA encoding CD300LF (CD300LF-mRNA-macrophage). Consistently, in a mouse model of acute liver failure, CD300LF-mRNA-macrophages facilitated organ recovery from acetaminophen-induced hepatotoxicity. These results demonstrate a GMP-compliant macrophage-manufacturing process and indicate that macrophages can be engineered by versatile mRNA technology to achieve therapeutic goals.
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Mule ducks accumulate a large amount of fat in their livers when fed high-energy feed, which is predominantly used for producing fatty livers. Nevertheless, there is limited research on the molecular mechanisms underlying the formation of fatty liver in mule ducks. Fatty acid translocase (CD36) is a sensor for fatty acids and lipid metabolism regulator, which may play a crucial role in the accumulation of fat in the liver of mule ducks. In this study, Overexpression and CD36 gene interference for 24 h was followed by induction of liver cells with 400 µmol/L palmitic acid (PA) for 24 h. The results demonstrated that CD36 overexpression increased hepatic triglyceride content, lipid droplet deposition, oxidative stress, and cell apoptosis. However, interference with CD36 had the opposite effect. CD36 overexpression suppressed the expression of AMPK and CPT-1A genes but enhanced the expression of ACC1 and LKB1 genes, with interference yielding contrasting results. Additionally, the expression of CD36 inhibited the AMPK pathway, reduced AMPK phosphorylation, downregulated AMPK protein expression, and upregulated SREBP1 protein expression. This promoted palmitic acid-induced hepatocyte fat accumulation. In summary, CD36 promotes palmitic acid-induced fat accumulation in primary mule duck liver cells through the AMPK signaling pathway.
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INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer after hepatocellular carcinoma. Through data mining of publicly available iCCA transcriptomic datasets from the Gene Expression Omnibus, we identified SFN as the most significantly up-regulated gene in iCCA compared to normal tissue, focusing on the Gene Ontology term "cell proliferation" (GO:0008283). SFN encodes the 14-3-3σ protein, also known as stratifin, which plays crucial roles in various cellular processes. MATERIALS AND METHODS: Immunohistochemistry was used to assess stratifin expression in 182 patients with localized iCCAs undergoing surgical resection. Patients were divided into low and high expression groups, and the association between stratifin expression and clinicopathological features was analyzed. Univariate and multivariate survival analyses were performed to assess overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS). RESULTS: Elevated stratifin expression in iCCAs was significantly associated with the absence of hepatitis, positive surgical margins, advanced primary tumor stages, and higher histological grades (all p ≤ 0.011). Survival analyses demonstrated a significant negative association between stratifin expression and all prognostic indicators, including OS, DSS, LRFS, and MeFS (all p ≤ 0.0004). Multivariate analysis revealed that stratifin overexpression was significantly correlated with poorer outcomes in terms of DSS, LRFS, and MeFS (all p < 0.001). CONCLUSIONS: These findings suggest that stratifin may play a crucial role in iCCA oncogenesis and tumor progression, serving as a potential novel prognostic biomarker.
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Phthalate acid esters (PAEs), as a common group of plasticizers, are widely present in indoor environments and pose a risk to human health. Indoor dust samples collected from dormitory, classroom, laboratory, and office in several universities in China, were analyzed for seven types of PAEs. The total concentrations of seven PAEs (Σ7PAEs) ranged from 4.87 to 360 µg/g, with a median concentration of 51 µg/g, which is lower than that reported by other studies. Using the median concentration of Σ7PAEs as a metric, we assessed the levels of contamination in different microenvironments, resulting in the following ranking: dormitory > classroom > laboratory > office. There are significant differences in the levels of individual PAEs in different microenvironments. Radiation from sunlight, ventilation rates, cleaning frequency, and sprays were influential factors for the concentrations of individual PAEs in indoor dust. The indoor environmental conditions and consumption patterns profoundly affect PAEs levels. The sources of PAEs in classroom and office were more complex than in dormitory and laboratory. Daily intakes of PAEs were used to calculate carcinogenic and non-carcinogenic human risk for males and females, indicating a low health risk to humans. This is the first study to assess the risk of PAEs in university microenvironments and provides a valuable reference for further research.
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Contaminación del Aire Interior , Polvo , Monitoreo del Ambiente , Ésteres , Ácidos Ftálicos , Ácidos Ftálicos/análisis , Contaminación del Aire Interior/análisis , Contaminación del Aire Interior/estadística & datos numéricos , Polvo/análisis , Humanos , Ésteres/análisis , Medición de Riesgo , Universidades , China , Plastificantes/análisis , Masculino , Femenino , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a Riesgos Ambientales/análisisRESUMEN
BACKGROUND: The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. METHODS: We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. RESULTS: 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p < 0.0001). Patients with greater SII-PNI scores had a poorer prognosis (p < 0.0001). The SII-PNI score was found to be an independent predictor of both overall survival (HR = 4.982, 95%CI: 1.890-10.234, p = 0.001) and disease-free survival (HR = 4.763, 95%CI: 1.994-13.903, p = 0.001) in a multivariate analysis. CONCLUSION: The clinical potential and accuracy of low-cost stratification based on SII-PNI score in forecasting tumor response and prognosis in LAGC is satisfactory.
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Terapia Neoadyuvante , Evaluación Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/inmunología , Masculino , Femenino , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inflamación , Estado Nutricional , Estudios Prospectivos , Quimioterapia Adyuvante/métodosRESUMEN
Background: Hematopoietic stem cell transplantation (HSCT) is one of the mainstream treatments for patients with hematologic malignancies. The matching status of human leukocyte antigen (HLA) between the donor and recipient is highly related to the outcomes of HSCT. Haploidentical HSCT (haplo-HSCT) has emerged as a type of HSCT for patients who cannot find a fully HLA-matched donor. In this study, we investigated whether the single nucleotide polymorphisms (SNPs) of the HLA-related genes and the genes encoding co-stimulatory molecules located on the non-HLA region are related to the outcomes of haplo-HSCT. Methods: The genomic DNAs of 24 patients and their respective donors were isolated from the peripheral blood obtained before performing haplo-HSCT. A total of 75 SNPs of the HLA-related genes (HCP5, NOTCH4, HLA-DOA, LTA, HSPA1L, BAG6, RING1, TRIM27, and HLA-DOB) and the genes located in the non-HLA genes involved in co-stimulatory signaling (CTLA4, TNFSF4, CD28, and PDCD1) were selected to explore their relationship with the outcomes after haplo-HSCT, including graft-versus-host disease, survival status, and relapse. Results: Our data revealed that specific donor or patient SNPs, including rs79327197 of the HLA-DOA gene, rs107822 and rs213210 of the RING1 gene, rs2523676 of the HCP5 gene, rs5742909 of the CTLA4 gene, rs5839828 and rs36084323 of the PDCD1 gene, and rs1234314 of the TNFSF4 gene, were significantly related to the development of adverse outcomes post-haplo-HSCT. Conclusions: These SNPs may play important roles in post-transplant immune response that can be considered during the selection of suitable donors.
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Livestock and poultry meat consumption play an important role in the dietary structure of Chinese residents. However, the extent of residues of veterinary drugs and heavy metal contamination in livestock and poultry meat and their by-products within Hunan province is not extensively studied. This survey aimed to fill this gap by assessing the presence of 76 veterinary drug residues in Hunan province. Additionally, heavy metals in pork and pig liver were also assessed. The obtained findings suggest that residues of veterinary drugs are still present in livestock and poultry meat, as well as their by-products, within Hunan province. However, the contamination of heavy metals remained within the food safety limits. These results underscore the significance of establishing more refined criteria for assessing human exposure, taking into account factors such as consumption patterns, product varieties and chemical compounds of interest.
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Cinnamomum cassia (L.) J.Presl, a tropical aromatic evergreen tree belonging to the Lauraceae family, is commonly used in traditional Chinese medicine. It is also a traditional spice used worldwide. However, little is currently known about the extent of the genetic variability and population structure of C. cassia. In this study, 71 individuals were collected from seven populations across two geographical provinces in China. Nine morphological features, three chemical components, and single nucleotide polymorphism (SNP) markers were used in an integrated study of C. cassia germplasm variations. Remarkable genetic variation exists in both phenotypic and chemical compositions, and certain traits, such as leaf length, leaf width, volatile oil content, and geographic distribution, are correlated with each other. One-year-old C. cassia seedling leaf length, leaf width, elevation, and volatile oil content were found to be the main contributors to diversity, according to principal component analysis (PCA). Three major groupings were identified by cluster analysis based on the phenotypic and volatile oil data. This was in line with the findings of related research using 1,387,213 SNP markers; crucially, they all demonstrated a substantial link with geographic origin. However, there was little similarity between the results of the two clusters. Analysis of molecular variance (AMOVA) revealed that the genetic diversity of C. Cassia populations was low, primarily among individuals within populations, accounting for 95.87% of the total. Shannon's information index (I) varied from 0.418 to 0.513, with a mean of 0.478 (Na=1.860, Ne =1.584, Ho =0.481, He =0.325, and PPB =86.04%). Genetic differentiation across populations was not significant because natural adaptation or extensive exchange of seeds among farmers between environments, thus maintaining the relationship. Following a population structure analysis using the ADMIXTURE software, 71 accessions were found to be clustered into three groups, with 38% of them being of the pure type, a finding that was further supported by PCA. Future breeding strategies and our understanding of the evolutionary relationships within the C. cassia population would benefit greatly from a thorough investigation of phenotypic, chemical, and molecular markers.
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INTRODUCTION: Kidney cancer ranks as the ninth most common cancer in men and the fourteenth in women globally, with renal cell carcinoma (RCC) being the most prevalent type. Despite advances in therapeutic strategies targeting angiogenesis and immune checkpoints, the absence of reliable markers for patient selection and limited duration of disease control underline the need for innovative approaches. CK1δ and CK1ε are highly conserved serine/threonine kinases involved in cell cycle regulation, apoptosis, and circadian rhythm. While CK1δ dysregulation is reportedly associated with breast and bladder cancer progression, their role in RCC remains elusive. This study aimed to investigate the feasibility of CK1δ/ε as new therapeutic targets for RCC patients. METHODS: The relationship between CK1δ/ε and RCC progression was evaluated by the analysis of microarray dataset and TCGA database. The anticancer activity of CK1δ/ε inhibitor was examined by MTT/SRB assay, and apoptotic cell death was analyzed by flow cytometry and Western blotting. RESULTS: Our data demonstrate that the gene expression of CSNK1D and CSNK1E is significantly higher in clear cell RCC (ccRCC) tissues compared to normal kidney samples, which is correlated with lower survival rates in ccRCC patients. SR3029, a selective inhibitor targeting CK1δ/ε, significantly suppresses the viability and proliferation of ccRCC cell lines regardless of the status of VHL deficiency. Importantly, the inhibitor promotes the population of subG1 cells and induces apoptosis, and ectopically expression of CK1δ partially rescued SR3029-induced apoptosis in ccRCC cells. CONCLUSION: These findings underscore the crucial role of CK1δ and CK1ε in ccRCC progression, suggesting CK1δ/ε inhibitors as new therapeutic options for ccRCC patients.
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In recent years, the toxic effects of microplastics (MPs) on aquatic organisms have been increasingly recognized. However, the developmental toxicity and underlying mechanisms of photoaged MPs at environmental concentrations remain unclear. Therefore, the photodegradation of pristine polystyrene (P-PS) under UV irradiation was used to investigate, as well as the developmental toxicity and underlying mechanisms of zebrafish (Danio rerio) exposed to P-PS and aged polystyrene (A-PS) at environmentally relevant concentrations (0.1-100 µg/L). Mortality, heart rate, body length, and tail coiling frequency of zebrafish larvae were the developmental toxicity endpoints. A-PS had increased crystallinity, the introduction of new functional groups, and higher oxygen content after UV-photoaging. The toxicity results showed that exposure to A-PS resulted in more adverse developmental toxicity than exposure to P-PS. Exposure to A-PS induced oxidative damage, as evidenced by elevated production of reactive oxygen species (ROS) and DNA damage, and led to decreased mitochondrial membrane potential (MMP) and causes the release of cytochrome c (cyt c) from the mitochondria. The caspase-3/-9 activation signaling pathways may cause developmental toxicity via mitochondrial apoptosis. Significant changes in the expression of genes were further explored linking with oxidative stress, mitochondria dysfunctions and apoptosis pathways following A-PS exposure. These findings underscore the importance of addressing the environmental applications of aged MPs and call for further research to mitigate their potential risks on aquatic ecosystems and human health.
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Apoptosis , Microplásticos , Mitocondrias , Estrés Oxidativo , Poliestirenos , Especies Reactivas de Oxígeno , Pez Cebra , Animales , Microplásticos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Poliestirenos/toxicidad , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Contaminantes Químicos del Agua/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Urban green spaces are the soil component in cities that interacts most closely with humans. This study investigated the residues of seven neonicotinoids (NEOs) in soils from urban green spaces within the Pearl River Delta (PRD) region and analyzed the correlation between the residue characteristics and the region's economic development. Notably, we introduced the Nemerow Index method, a comprehensive approach, to quantify the overall pollution level of NEOs in the soil of urban park green spaces and utilized this to assess the cumulative exposure probability risks for different populations in this scenario. We found that: (1) The soil of urban park green spaces exhibited varying degrees of NEOs contamination (Σ7NEOs: N.D.-137.31; 6.25 µg/kg), with imidacloprid and clothianidin constituting the highest proportions (89.46 % and 83.60 %); (2) The residual levels of NEOs in Children's Park were significantly higher than those in community parks within Guangzhou, with an average value of 13.30 µg/kg compared to 3.30 µg/kg; (3) The residual characteristics of NEOs exhibited a positive correlation with regional economic development; specifically, the per capita GDP well correlated with IMIRPF, a summation of seven NEOs in imidacloprid equivalents via relative potency factors (R2 =0.86). Regions with higher economic development typically exhibited elevated IMIRPF levels; (4) The fitted cumulative probability distributions for average daily exposure doses revealed that children's exposure was an order of magnitude higher than adults'. Despite this, the exposure risks for both groups remained within acceptable limits.
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Insecticidas , Neonicotinoides , Contaminantes del Suelo , Neonicotinoides/análisis , Neonicotinoides/toxicidad , China , Medición de Riesgo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/toxicidad , Insecticidas/análisis , Insecticidas/toxicidad , Humanos , Ciudades , Monitoreo del Ambiente , Factores Socioeconómicos , Parques Recreativos , Ríos/química , Residuos de Plaguicidas/análisis , Residuos de Plaguicidas/toxicidadRESUMEN
Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.
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Adenosina , Metástasis Linfática , ARN Circular , Proteínas de Unión al ARN , Transducción de Señal , Neoplasias Gástricas , Factor A de Crecimiento Endotelial Vascular , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Metástasis Linfática/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Animales , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Transducción de Señal/genética , Ratones , Masculino , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Pronóstico , Femenino , Ratones DesnudosRESUMEN
Sediment is the ultimate sink of environmental pollutants. A total of 128 surface sediment samples were collected from 8 rivers and 3 reservoirs in Maoming City, Guangdong Province. This study assessed the content and distribution of brominated flame retardants in sediments. The acute toxicity effects of tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDs) in sediments were evaluated using Caenorhabditis elegans as model organisms. The concentration of TBBPA in sediments ranged from not detected (ND) to 12.59 µg/kg and was mainly distributed in the central area, which was affected by the emission of TBBPA from residential and factory. The concentration of HBCDs ranged from ND to 6.31 µg/kg, and the diastereoisomer distribution was consistent, showing a trend close to the South China Sea. The composition pattern of HBCDs in the surface sediments from rivers were 41.73%-62.33%, 7.89%-25.54%, and 18.76%-40.65% for α-, ß-, and γ-HBCD, respectively, and in the sediments from reservoirs were 26.15%-45.52%, 7.44%-19.23%, and 47.04%-61.89% for α-, ß-, and γ-HBCD, respectively. When the sum of concentrations of TBBPA and HBCD in sediments were above high levels, reactive oxygen species in nematodes significantly increased, resulting in an oxidative stress response. Intestinal permeability was also enhanced, causing intestinal damage. In addition, in terms of this study, TBBPA had a greater impact on biotoxicity compared to HBCDs, and more attention should be paid to the toxic effects of the river ecosystem organisms in Maoming City, Guangdong Province. This study can complement the pollution database in the study area and provide basic data for pollution control.
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Caenorhabditis elegans , Monitoreo del Ambiente , Retardadores de Llama , Sedimentos Geológicos , Hidrocarburos Bromados , Contaminantes Químicos del Agua , Animales , Retardadores de Llama/toxicidad , Retardadores de Llama/análisis , China , Caenorhabditis elegans/efectos de los fármacos , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Hidrocarburos Bromados/análisis , Hidrocarburos Bromados/toxicidad , Bifenilos Polibrominados/toxicidad , Bifenilos Polibrominados/análisisRESUMEN
Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the recurrent metastatic patterns and prognostic factors in AFPGC patients undergoing radical surgical resection. Data from 241 AFPGC patients diagnosed between January 2017 and January 2020 who underwent surgical resection were analyzed across multiple centers. Recurrence patterns, metastatic sites, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify risk factors for recurrent metastasis, overall survival (OS), and disease-free survival (DFS). There is an annual increase in the proportion of AFPGC cases, rising from 3.45% in 2017 to 7.88% in 2023. Higher serum AFP level was associated with increased likelihood of lymph node metastasis (P=0.006), deeper invasion depth (P=0.000) and greater tumor diameter (P=0.036). Independent predictors of recurrent metastasis included T4 infiltration, lymph node metastasis, tumor diameter >5 cm, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP levels. The 5-year OS and DFS rates were 36.5% and 34.2%, respectively, with poorer survival linked to higher preoperative AFP levels and postoperative increasing trend in AFP level. Independent risk factors for poor OS and DFS included T4 infiltration, lymph node metastasis, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP. Serum AFP level can serve as a potential predictive and prognostic biomarker. Identifying independent risk factors informs risk stratification and personalized treatment for AFPGC patients.
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OBJECTIVE: To establish nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer liver metastasis (GCLM) patients. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database for 5,451 GCLM patients diagnosed between 2010 and 2015 were analyzed. The cohort was divided into a training set (3,815 cases) and an internal validation set (1,636 cases). External validation included 193 patients from the Fourth Hospital of Hebei Medical University and 171 patients from the People's Hospital of Shijiazhuang City, spanning 2016-2018. Multivariable Cox regression analysis identified eight independent prognostic factors for OS and CSS in GCLM patients, including age, histological type, grade, tumor size, surgery, chemotherapy, bone metastasis, and lung metastasis. Two nomogram models were developed based on these factors and evaluated using time-dependent receiver operating characteristic curve analysis, calibration curves, and decision curve analysis. RESULTS: Internal validation showed that the nomogram models outperformed the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system in predicting 1-year, 2-year, and 3-year OS and CSS in GCLM patients (1-year OS: 0.801 vs. 0.593, P < 0.001; 1-year CSS: 0.807 vs. 0.598, P < 0.001; 2-year OS: 0.803 vs. 0.630, P < 0.001; 2-year CSS: 0.802 vs. 0.633, P < 0.001; 3-year OS: 0.824 vs. 0.691, P < 0.001; 3-year CSS: 0.839 vs. 0.692, P < 0.001). CONCLUSION: This study developed and validated nomogram models using SEER database data to predict OS and CSS in GCLM patients. These models offer improved prognostic accuracy over traditional staging systems, aiding in clinical decision-making.
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Introduction: Lymph node (LN) status is a vital prognostic factor for patients. However, there has been limited focus on predicting the prognosis of patients with late-onset gastric cancer (LOGC). This study aimed to investigate the predictive potential of the log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in assessing the prognosis of patients diagnosed with LOGC. Methods: The LOGC data were obtained from the Surveillance, Epidemiology, and End Results database. This study evaluated and compared the predictive performance of three LN staging systems. Univariate and multivariate Cox regression analyses were carried out to identify prognostic factors for overall survival (OS). Three machine learning methods, namely, LASSO, XGBoost, and RF analyses, were subsequently used to identify the optimal LN staging system. A nomogram was built to predict the prognosis of patients with LOGC. The efficacy of the model was demonstrated through receiver operating characteristic (ROC) curve analysis and decision curve analysis. Results: A total of 4,743 patients with >16 removed lymph nodes were ultimately included in this investigation. Three LN staging systems demonstrated significant performance in predicting survival outcomes (P < 0.001). The LNR exhibited the most important prognostic ability, as evidenced by the use of three machine learning methods. Utilizing independent factors derived from multivariate Cox regression analysis, a nomogram for OS was constructed. Discussion: The calibration, C-index, and AUC revealed their excellent predictive performance. The LNR demonstrated a more powerful performance than other LN staging methods in LOGC patients after surgery. Our novel nomogram exhibited superior clinical feasibility and may assist in patient clinical decision-making.
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This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.