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BACKGROUND: Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance. METHODS: Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses. RESULTS: A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value. CONCLUSIONS: Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis.
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Anemia , Nomogramas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Masculino , Feminino , Anemia/etiologia , Anemia/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Fatores de Risco , Seguimentos , Gastrectomia , Idoso , Estadiamento de Neoplasias , Curva ROC , Período Pré-Operatório , AdultoRESUMO
BACKGROUND: The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway. METHODS: In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing. RESULTS: P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris's water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements. CONCLUSIONS: We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.
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Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Animais , Camundongos , Masculino , Reabilitação Neurológica/métodos , Prevotella , Microbioma Gastrointestinal/fisiologia , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
Intestinal microbiome contains several times of functional genes compared to the host and mediates the generation of multiple metabolic products, and therefore it is called "second genome" for host. Crustaceans rank second among the largest subphylum of aquaculture animals that are considered potentially satisfy global substantial food and nutrition security, among which the Pacific white shrimp (Litopenaeus vannamei) ranks the first in the production. Currently, increasing evidences show that outbreaks of some most devastating diseases in shrimp, including white feces syndrome (WFS) and acute hepatopancreatic necrosis disease (AHPND), are related to intestinal microbiota dysbiosis. Importantly, the intestine microbial composition can be altered by environmental stress, diet, and age. In this review, we overview the progress of intestinal microbiota dysbiosis and WFS or ANPHD in shrimp, and how the microbial composition is altered by external factors. Hence, developing suitable microbial micro-ecological prevention and control strategy to maintain intestinal balance may be a feasible solution to reduce the risk of disease outbreaks. Moreover, we highlight that defining the "healthy intestine microbiota" and evaluating the causality of intestinal microbiota dysbiosis and diseases following the logic of "Microecological Koch's postulates" should be the key goal in future shrimp intestinal field, which help to guide disease diagnosis and prevent disease outbreaks in shrimp farming. KEY POINTS: ⢠Intestinal microbiota dysbiosis is relevant to multiple shrimp diseases. ⢠Microecological Koch's postulates help to evaluate the causality of shrimp diseases.
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Aquicultura , Disbiose , Microbioma Gastrointestinal , Penaeidae , Animais , Penaeidae/microbiologia , Disbiose/microbiologiaRESUMO
Drug repurposing offers a viable strategy for discovering new drugs and therapeutic targets through the analysis of drug-gene interactions. However, traditional experimental methods are plagued by their costliness and inefficiency. Despite graph convolutional network (GCN)-based models' state-of-the-art performance in prediction, their reliance on supervised learning makes them vulnerable to data sparsity, a common challenge in drug discovery, further complicating model development. In this study, we propose SGCLDGA, a novel computational model leveraging graph neural networks and contrastive learning to predict unknown drug-gene associations. SGCLDGA employs GCNs to extract vector representations of drugs and genes from the original bipartite graph. Subsequently, singular value decomposition (SVD) is employed to enhance the graph and generate multiple views. The model performs contrastive learning across these views, optimizing vector representations through a contrastive loss function to better distinguish positive and negative samples. The final step involves utilizing inner product calculations to determine association scores between drugs and genes. Experimental results on the DGIdb4.0 dataset demonstrate SGCLDGA's superior performance compared with six state-of-the-art methods. Ablation studies and case analyses validate the significance of contrastive learning and SVD, highlighting SGCLDGA's potential in discovering new drug-gene associations. The code and dataset for SGCLDGA are freely available at https://github.com/one-melon/SGCLDGA.
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Redes Neurais de Computação , Humanos , Reposicionamento de Medicamentos/métodos , Biologia Computacional/métodos , Algoritmos , Software , Descoberta de Drogas/métodos , Aprendizado de MáquinaRESUMO
The interaction between the gut and the liver plays a significant role in individual health and diseases. Mounting evidence supports that bile acids are important metabolites in the bidirectional communication between the gut and the liver. Most of the current studies on the "gut-liver axis" have focused on higher vertebrates, however, few was reported on lower invertebrates such as shrimp with an open circulatory system. Here, microbiomic and metabolomic analyses were conducted to investigate the bacterial composition and bile acid metabolism in intestine, hemolymph and hepatopancreas of Penaeus vannamei fed diets supplemented with octanoic acid and oleic acid. After six days of feeding, the bacterial composition in intestine, hemolymph and hepatopancreas changed at different stages, with significant increases in the relative abundance of several genera such as Pseudomonas and Rheinheimera in intestine and hepatopancreas. Notably, there was a more similar bacterial composition in intestine and hepatopancreas at the genus level, which indicated the close communication between shrimp intestine and hepatopancreas. Meanwhile, higher content of some bile acids such as lithocholic acid (LCA) and α-muricholic acid (α-MCA) in intestine and lower content of some bile acids such as taurohyocholic acids (THCA) and isolithocholic acid (IsoLCA) in hepatopancreas were detected. Furthermore, Spearman correlation analysis revealed a significant correlation between bacterial composition and bile acid metabolism in intestine and hepatopancreas. The microbial source tracking analysis showed that there was a high proportion of intestine and hepatopancreas bacterial community as the source of each other. Collectively, these results showed a strong crosstalk between shrimp intestine and hepatopancreas, which suggests a unique potential "intestine-hepatopancreas axis" in lower invertebrate shrimp with an open circulatory system. Our finding contributed to the understanding of the interplay between shrimp intestine and hepatopancreas in the view of microecology and provided new ideas for shrimp farming and disease control.
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Ácidos e Sais Biliares , Hepatopâncreas , Penaeidae , Animais , Penaeidae/metabolismo , Penaeidae/microbiologia , Hepatopâncreas/metabolismo , Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal/fisiologia , Intestinos/microbiologia , Bactérias/metabolismoRESUMO
Solubility is not only a significant physical property of molecules but also a vital factor in smallmolecule drug development. Determining drug solubility demands stringent equipment, controlled environments, and substantial human and material resources. The accurate prediction of drug solubility using computational methods has long been a goal for researchers. In this study, we introduce MSCSol, a solubility prediction model that integrates multidimensional molecular structure information. We incorporate a graph neural network with geometric vector perceptrons (GVP-GNN) to encode 3D molecular structures, representing spatial arrangement and orientation of atoms, as well as atomic sequences and interactions. We also employ Selective Kernel Convolution combined with Global and Local attention mechanisms to capture molecular features context at different scales. Additionally, various descriptors are calculated to enrich the molecular representation. For the 2D and 3D structural data of molecules, we design different data augmentation strategies to enhance generalization ability and prevent the model from learning irrelevant information. Extensive experiments on benchmark and independent datasets demonstrate MSCSol's superior performance. Ablation studies further confirm the effectiveness of different modules. Interpretability analysis highlights the importance of various atomic groups and substructures for solubility and verifies that our model effectively captures functional molecular structures and higher-order knowledge. The source code and datasets are freely available at https://github.com/ZiyuFanCSU/MSCSol.
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OBJECTIVES: The absence of non-invasive biomarkers for the early diagnosis of colorectal cancer (CRC) has contributed to poor prognosis. Extracellular vesicles (EVs) have emerged as promising candidates for cancer monitoring using liquid biopsy. However, the complexity of EVs isolation procedures and the absence of clear targets for detecting serum-derived EVs have hindered the clinical application of EVs in early CRC diagnosis. METHODS: In the discovery phase, we conducted a comprehensive 4D-DIA proteomic analysis of serum-derived EVs samples from 37 individuals, performing an initial screening of EVs surface proteins. In the technical validation phase, we developed an extraction-free CRC-EVArray microarray to assess the expression of these potential EVs surface proteins in a multi-centre study comprising 404 individuals. In the application phase, the authors evaluated the diagnostic efficacy of the CRC-EVArray model based on machine-learning algorithms. RESULTS: Through 4D-DIA proteomic analysis, the authors identified seven potential EVs surface proteins showing significantly differential expression in CRC patients compared to healthy controls. Utilizing our developed high-throughput CRC-EVArray microarray, we further confirmed the differential expression of three EVs surface proteins, FIBG, PDGF-ß and TGF-ß, in a large sample population. Moreover, we established an optimal CRC-EVArray model using the NNET algorithm, demonstrating superior diagnostic efficacy with an area under the curve (AUC) of 0.882 in the train set and 0.937 in the test set. Additionally, we predicted the functions and potential origins of these EVs-derived proteins through a series of multi-omics approaches. CONCLUSIONS: Our systematic exploration of surface protein expression profiles on serum-derived EVs has identified FIBG, PDGF-ß, and TGF-ß as novel diagnostic biomarkers for CRC. The development of CRC-EVArray diagnostic model based on these findings provided an effective tool for the large-scale CRC screening, thus facilitating its translation into clinical practice.
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Biomarcadores Tumorais , Neoplasias Colorretais , Vesículas Extracelulares , Proteômica , Fator de Crescimento Transformador beta , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Vesículas Extracelulares/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Proteômica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Idoso , Proteínas Proto-Oncogênicas c-sis/análise , Proteínas Proto-Oncogênicas c-sis/metabolismo , Proteínas Proto-Oncogênicas c-sis/sangue , Proteínas de Membrana/sangue , Proteínas de Membrana/metabolismoRESUMO
Introduction: Elite athletes' help-seeking on mental health might be influenced by their mental health literacy (MHL) and mental health experiences. The current study aimed to explore the MHL, experiences and help-seeking behaviours among elite athletes using a qualitative approach. Methods: Face-to-face semi-structured interviews were conducted among 20 Chinese elite athletes, 12 coaches, and 5 team officials. Interview data was analyzed using content analysis. Results: Seven main themes emerged from the analysis. The current study revealed that Chinese elite athletes suffered from various mental health issues and athletes' MHL levels, help-seeking attitudes and intentions, Chinese sports environments, and Chinese cultural background could impact their help-seeking behaviours. Conclusion: Support for Chinese elite athletes' mental health and help-seeking requires improvement.
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Atletas , Letramento em Saúde , Comportamento de Busca de Ajuda , Saúde Mental , Pesquisa Qualitativa , Humanos , Atletas/psicologia , Masculino , Feminino , China , Adulto , Adulto Jovem , Entrevistas como Assunto , Adolescente , População do Leste AsiáticoRESUMO
Extracellular vesicles (EVs) were promising circulating biomarkers for multiple diseases, but whether serum EVs-derived proteins could be used as a reliable tumor biomarker for colorectal cancer (CRC) remained inconclusive. In this study, we identified CXCL4 by a 4D data-independent acquisition-based quantitative proteomics assay of serum EVs-derived proteins in 40 individuals and subsequently analyzed serum EVs-derived CXCL4 levels by ELISA in 2 cohorts of 749 individuals. The results revealed that EVs-derived CXCL4 levels were dramatically elevated in CRC patients than in benign colorectal polyp patients or healthy controls (HC). Furthermore, receiver operating characteristic curves revealed that EVs-derived CXCL4 exhibited superior diagnostic performance with area under the curve of 0.948 in the training cohort. Additionally, CXCL4 could effectively distinguish CRC in stage I/II from HC. Notably, CRC patients with high levels of EVs-derived CXCL4 have shorter 2-year progression-free survival than those with low levels. Overall, our findings demonstrated that serum EVs-derived CXCL4 was a candidate diagnostic and prognostic biomarker for CRC.
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In the present study, small RNA (sRNA) data from Ascosphaera apis were filtered from sRNA-seq datasets from the gut tissues of A. apis-infected Apis mellifera ligustica worker larvae, which were combined with the previously gained sRNA-seq data from A. apis spores to screen differentially expressed milRNAs (DEmilRNAs), followed by trend analysis and investigation of the DEmilRNAs in relation to significant trends. Additionally, the interactions between the DEmilRNAs and their target mRNAs were verified using a dual-luciferase reporter assay. In total, 974 A. apis milRNAs were identified. The first base of these milRNAs was biased toward U. The expression of six milRNAs was confirmed by stem-loop RT-PCR, and the sequences of milR-3245-y and milR-10285-y were validated using Sanger sequencing. These miRNAs grouped into four significant trends, with the target mRNAs of DEmilRNAs involving 42 GO terms and 120 KEGG pathways, such as the fungal-type cell wall and biosynthesis of secondary metabolites. Further investigation demonstrated that 299 DEmilRNAs (novel-m0011-3p, milR-10048-y, bantam-y, etc.) potentially targeted nine genes encoding secondary metabolite-associated enzymes, while 258 (milR-25-y, milR-14-y, milR-932-x, etc.) and 419 (milR-4561-y, milR-10125-y, let-7-x, etc.) DEmilRNAs putatively targeted virulence factor-encoded genes and nine genes involved in the MAPK signaling pathway, respectively. Additionally, the interaction between ADM-B and milR-6882-x, as well as between PKIA and milR-7009-x were verified. Together, these results not only offer a basis for clarifying the mechanisms underlying DEmilRNA-regulated pathogenesis of A. apis and a novel insight into the interaction between A. apis and honey bee larvae, but also provide candidate DEmilRNA-gene axis for further investigation.
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BACKGROUND: White matter injury (WMI) is an important pathological process after traumatic brain injury (TBI). The correlation between white matter functions and the myeloid cells expressing triggering receptor-2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism is crucial for early remyelination after demyelinating diseases. However, the potential roles of TREM2 expression and microglial sterol metabolism in WMI after TBI have not yet been explored. METHODS: Controlled cortical injury was induced in both wild-type (WT) and TREM2 depletion (TREM2 KO) mice to simulate clinical TBI. COG1410 was used to upregulate TREM2, while PLX5622 and GSK2033 were used to deplete microglia and inhibit the liver X receptor (LXR), respectively. Immunofluorescence, Luxol fast blue staining, magnetic resonance imaging, transmission electron microscopy, and oil red O staining were employed to assess WMI after TBI. Neurological behaviour tests and electrophysiological recordings were utilized to evaluate cognitive functions following TBI. Microglial cell sorting and transcriptomic sequencing were utilized to identify alterations in microglial sterol metabolism-related genes, while western blot was conducted to validate the findings. RESULTS: TREM2 expressed highest at 3 days post-TBI and was predominantly localized to microglial cells within the white matter. Depletion of TREM2 worsened aberrant neurological behaviours, and this phenomenon was mediated by the exacerbation of WMI, reduced renewal of oligodendrocytes, and impaired phagocytosis ability of microglia after TBI. Subsequently, the upregulation of TREM2 alleviated WMI, promoted oligodendrocyte regeneration, and ultimately facilitated the recovery of neurological behaviours after TBI. Finally, the expression of DHCR24 increased in TREM2 KO mice after TBI. Interestingly, TREM2 inhibited DHCR24 and upregulated members of the LXR pathway. Moreover, LXR inhibition could partially reverse the effects of TREM2 upregulation on electrophysiological activities. CONCLUSIONS: We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia.
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Lesões Encefálicas Traumáticas , Glicoproteínas de Membrana , Microglia , Receptores Imunológicos , Substância Branca , Animais , Masculino , Camundongos , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Modelos Animais de Doenças , Receptores X do Fígado/metabolismo , Receptores X do Fígado/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Substância Branca/metabolismo , Substância Branca/patologiaRESUMO
Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.
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BACKGROUND: The progression of tumors from less aggressive subtypes to more aggressive states during metastasis poses challenges for treatment strategies. Previous studies have revealed the molecular subtype conversion between primary and metastatic tumors in breast cancer (BC). However, the subtype conversion during lymph node metastasis (LNM) and the underlying mechanism remains unclear. METHODS: We compared clinical subtypes in paired primary tumors and positive lymph nodes (PLNs) in BC patients and further validated them in the mouse model. Bioinformatics analysis and macrophage-conditioned medium treatment were performed to investigate the role of macrophages in subtype conversion. RESULTS: During LNM, hormone receptors (HRs) were down-regulated, while HER2 was up-regulated, leading to the transformation of luminal A tumors towards luminal B tumors and from luminal B subtype towards HER2-enriched (HER2-E) subtype. The mouse model demonstrated the elevated levels of HER2 in PLN while retaining luminal characteristics. Among the various cells in the tumor microenvironment (TME), macrophages were the most clinically relevant in terms of prognosis. The treatment of a macrophage-conditioned medium further confirmed the downregulation of HR expression and upregulation of HER2 expression, inducing tamoxifen resistance. Through bioinformatics analysis, MNX1 was identified as a potential transcription factor governing the expression of HR and HER2. CONCLUSION: Our study revealed the HER2-E subtype conversion during LNM in BC. Macrophages were the crucial cell type in TME, inducing the downregulation of HR and upregulation of HER2, probably via MNX1. Targeting macrophages or MNX1 may provide new avenues for endocrine therapy and targeted treatment of BC patients with LNM.
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The role of RNA methylation is vital in the advancement and spread of tumors. However, its exact role in microsatellite instability in colorectal cancer (CRC) is still not fully understood. To address this gap in knowledge, this study investigated the impact of genes associated with RNA methylation on the prognosis and response to immunotherapy in individuals diagnosed with low microsatellite instability (MSI-L) or microsatellite stable (MSS) CRC. The differentially expressed genes (DEGs) in two groups of patients: those with high microsatellite instability (MSI-H) and those with MSI-L/MSS was thoroughly investigated and compared with aims of exploring the association between them and the 60 RNA methylation regulators. We employed these genes and developed an MSI-RMscore to establish a risk signature capable of forecasting patient outcomes. Furthermore, an investigation of the immunophenotypic traits was conducted encompassing patients categorized as high-risk and low-risk. By combining the MSI-RMscore and clinicopathological features, a predictive nomogram was developed, which was subsequently validated using the GEO database. Furthermore, immunohistochemistry was employed to establish the correlation between INHBB and SOWAHA and the MSI status, as well as patient prognosis. Our findings indicated that the high-risk subgroup exhibited unfavorable overall survival rates, reduced responsiveness to immune checkpoint blockers, elevated estimate scores, and increased infiltration of macrophages and fibroblasts. We also confirmed that INHBB and SOWAHA were associated with CRC patient prognosis and MSI status, as well as immunotherapy response. These findings suggest that targeting INHBB and SOWAHA could be a promising strategy to enhance patient responsiveness to immunotherapy.
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Biomarcadores Tumorais , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Imunoterapia , Instabilidade de Microssatélites , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Prognóstico , Biomarcadores Tumorais/genética , Imunoterapia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Nomogramas , Metilação de DNA , Metilação de RNARESUMO
Increasing evidence suggests that intestine microorganisms are closely related to shrimp growth, but there is no existing experiment to prove this hypothesis. Here, we compared the intestine bacterial community of fast- and slow-growing shrimp at the same developmental stage with a marked difference in body size. Our results showed that the intestine bacterial communities of slow-growing shrimp exhibited less diversity but were more heterogeneous than those of fast-growing shrimp. Uncultured_bacterium_g_Candidatus Bacilloplasma, Tamlana agarivorans, Donghicola tyrosinivorans, and uncultured_bacterium_f_Flavobacteriaceae were overrepresented in the intestines of fast-growing shrimp, while Shimia marina, Vibrio sp., and Vibrio campbellii showed the opposite trends. We further found that the bacterial community composition was significantly correlated with shrimp length, and some bacterial species abundances were found to be significantly correlated with shrimp weight and length, including T. agarivorans and V. campbellii, which were chosen as indicators for a reverse gavage experiment. Finally, T. agarivorans was found to significantly promote shrimp growth after the experiment. Collectively, these results suggest that intestine bacterial community could be important factors in determining the growth of shrimp, indicating that specific bacteria could be tested in further studies against shrimp growth retardation. KEY POINTS: ⢠A close relationship between intestine bacterial community and shrimp growth was proven by controllable experiments. ⢠The bacterial signatures of the intestine were markedly different between slow- and fast-growing shrimp, and the relative abundances of some intestine bacterial species were correlated significantly with shrimp body size. ⢠Reverse gavage by Tamlana agarivorans significantly promoted shrimp growth.
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Alteromonadaceae , Penaeidae , Animais , Alimentos MarinhosRESUMO
PURPOSE: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. METHODS: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study's primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. RESULTS: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects. CONCLUSIONS: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib.
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Síndrome Mão-Pé , Hipertensão , Leucopenia , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Protocolos ClínicosRESUMO
Long non-coding RNAs (lncRNAs) are crucial modulators in a variety of biological processes, such as gene expression, development, and immune defense. However, little is known about the function of lncRNAs in the development of Asian honey bee (Apis cerana) larval guts. Here, on the basis of our previously obtained deep-sequencing data from the 4-, 5-, and 6-day-old larval guts of A. cerana workers (Ac4, Ac5, and Ac6 groups), an in-depth transcriptome-wide investigation was conducted to decipher the expression pattern, regulatory manners, and potential roles of lncRNAs during the developmental process of A. cerana worker larval guts, followed by the verification of the relative expression of differentially expressed lncRNAs (DElncRNAs) and the targeting relationships within a competing endogenous RNA (ceRNA) axis. In the Ac4 vs. Ac5 and Ac5 vs. Ac6 comparison groups, 527 and 498 DElncRNAs were identified, respectively, which is suggestive of the dynamic expression of lncRNAs during the developmental process of larval guts. A cis-acting analysis showed that 330 and 393 neighboring genes of the aforementioned DElncRNAs were respectively involved in 29 and 32 functional terms, such as cellular processes and metabolic processes; these neighboring genes were also respectively engaged in 246 and 246 pathways such as the Hedgehog signaling pathway and the Wnt signaling pathway. Additionally, it was found that 79 and 76 DElncRNAs as potential antisense lncRNAs may, respectively, interact with 72 and 60 sense-strand mRNAs. An investigation of competing endogenous RNA (ceRNA) networks suggested that 75 (155) DElncRNAs in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group could target 7 (5) DEmiRNAs and further bind to 334 (248) DEmRNAs, which can be annotated to 33 (29) functional terms and 186 (210) pathways, including 12 (16) cellular- and humoral-immune pathways (lysosome pathway, necroptosis, MAPK signaling pathway, etc.) and 11 (10) development-associated signaling pathways (Wnt, Hippo, AMPK, etc.). The RT-qPCR detection of five randomly selected DElncRNAs confirmed the reliability of the used sequencing data. Moreover, the results of a dual-luciferase reporter assay were indicative of the binding relationship between MSTRG.11294.1 and miR-6001-y and between miR-6001-y and ncbi_107992440. These results demonstrate that DElncRNAs are likely to modulate the developmental process of larval guts via the regulation of the source genes' transcription, interaction with mRNAs, and ceRNA networks. Our findings not only yield new insights into the developmental mechanism underlying A. cerana larval guts, but also provide a candidate ceRNA axis for further functional dissection.
Assuntos
MicroRNAs , RNA Longo não Codificante , Abelhas/genética , Animais , Larva/genética , Larva/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Hedgehog/genética , Reprodutibilidade dos Testes , RNA Mensageiro/genética , Redes Reguladoras de Genes , MicroRNAs/genéticaRESUMO
OBJECTIVES: Athlete burnout is a maladaptive outcome that is potentially detrimental for performance and wellbeing. Cross-sectional evidence suggests that mindfulness might be associated with athlete burnout via experiential avoidance and cognitive fusion. In the current study, we extend knowledge of these hypothesized mediational pathways using a longitudinal design. METHODS: Data was collected at three occasions with a three-month interval. A final sample of 280 elite Chinese athletes aged 15-32 years (Mage = 19.13; SD = 2.92; Female = 130) reported their mindfulness at Time 1, experiential avoidance and cognitive fusion at Time 2, and athlete burnout at Time 3. Structural equation modelling was adopted to examine the mediating roles of experiential avoidance and cognitive fusion on the effects from mindfulness to athlete burnout. RESULTS: We found statistically meaningful directs effects from mindfulness (Time 1) to experiential avoidance and cognitive fusion (Time 2), which in turn influenced athlete burnout (Time 3). However, the direct effect from mindfulness at Time 1 to athlete burnout at Time 3 was non-significant. The indirect effects of experiential avoidance and cognitive fusion on the effects from mindfulness to athlete burnout were significant, providing longitudinal evidence that these two variables contribute meaningfully to the mindfulness-burnout pathway. CONCLUSION: With initial evidence for the mediating effects of experiential avoidance and cognitive fusion, future studies could consider using experimental designs to examine the potential changing mechanisms of mindfulness on reducing athlete burnout.