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Scientific Reports Jun 2024Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into...
Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.
Topics: Humans; Cullin Proteins; Female; Prognosis; Breast Neoplasms; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Gene Expression Profiling; MCF-7 Cells; Triple Negative Breast Neoplasms
PubMed: 38942922
DOI: 10.1038/s41598-024-65692-z -
Communications Biology Jun 2024Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes...
Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes to late-stage diagnoses and poor survival. Highly vascularized and immune infiltrated microenvironment are prominent features of ccRCC, yet the interplay between vasculature and immune cells, disease progression and response to therapy remains poorly understood. Using droplet-based single-cell RNA sequencing we profile 50,236 transcriptomes from paired tumor and healthy adjacent kidney tissues. Our analysis reveals significant heterogeneity and inter-patient variability of the tumor microenvironment. Notably, we discover a previously uncharacterized vasculature subpopulation associated with epithelial-mesenchymal transition. The cell-cell communication analysis reveals multiple modes of immunosuppressive interactions within the tumor microenvironment, including clinically relevant interactions between tumor vasculature and stromal cells with immune cells. The upregulation of the genes involved in these interactions is associated with worse survival in the TCGA KIRC cohort. Our findings demonstrate the role of tumor vasculature and stromal cell populations in shaping the ccRCC microenvironment and uncover a subpopulation of cells within the tumor vasculature that is associated with an angiogenic phenotype.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Single-Cell Analysis; Tumor Microenvironment; Gene Expression Profiling; Phenotype; Gene Expression Regulation, Neoplastic; Endothelial Cells; Transcriptome; Epithelial-Mesenchymal Transition; Male; Female
PubMed: 38942917
DOI: 10.1038/s42003-024-06478-x -
Scientific Reports Jun 2024The Ediacaran-Cambrian transition documents a critical stage in the diversification of animals. The global fossil record documents the appearance of cloudinomorphs and...
The Ediacaran-Cambrian transition documents a critical stage in the diversification of animals. The global fossil record documents the appearance of cloudinomorphs and other shelled tubular organisms followed by non-biomineralized small carbonaceous fossils and by the highly diversified small shelly fossils between ~ 550 and 530 Ma. Here, we report diverse microfossils in thin sections and hand samples from the Ediacaran Bocaina Formation, Brazil, separated into five descriptive categories: elongate solid structures (ES); elongate filled structures (EF); two types of equidimensional structures (EQ 1 and 2) and elongate hollow structures with coiled ends (CE). These specimens, interpreted as diversified candidate metazoans, predate the latest Ediacaran biomineralized index macrofossils of the Cloudina-Corumbella-Namacalathus biozone in the overlying Tamengo Formation. Our new carbonate U-Pb ages for the Bocaina Formation, position this novel fossil record at 571 ± 9 Ma (weighted mean age). Thus, our data point to diversification of metazoans, including biomineralized specimens reminiscent of sections of cloudinids, protoconodonts, anabaritids, and hyolithids, in addition to organo-phosphatic surficial coverings of animals, demonstrably earlier than the record of the earliest known skeletonized metazoan fossils.
Topics: Fossils; Animals; Brazil; Animal Shells; Biological Evolution; Paleontology
PubMed: 38942912
DOI: 10.1038/s41598-024-65671-4 -
Scientific Reports Jun 2024Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae...
Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae are responsible for the unequal distribution of worms in natural host populations and thus investigated a susceptible versus a resistant mouse strain. In mice, the roundworm larvae develop until the lung stage and thus early anti-Ascaris immune responses against the migrating larvae in the liver and lung can be deciphered. Our data show that susceptible C57BL/6 mice respond to Ascaris larval migration significantly stronger compared to resistant CBA mice and the anti-parasite reactivity is associated with pathology. Increased eosinophil recruitment was detected in the liver and lungs, but also in the spleen and peritoneal cavity of susceptible mice on day 8 post infection compared to resistant mice. In serum, eosinophil peroxidase levels were significantly higher only in the susceptible mice, indicating functional activity of the recruited eosinophils. This effect was associated with an increased IL-5/IL-13 production by innate lymphoid cells and CD4 T cells and a pronounced type 2 macrophage polarization in the lungs of susceptible mice. Furthermore, a comparison of wildtype BALB/c and eosinophil-deficient dblGATA-1 BALB/c mice showed that eosinophils were not essential for the early control of migrating Ascaris larvae. In conclusion, in primary infection, a strong local and systemic type 2 immune response during hepato-tracheal helminth larval migration is associated with pathology rather than protection.
Topics: Animals; Ascariasis; Larva; Mice; Th2 Cells; Mice, Inbred BALB C; Lung; Ascaris; Eosinophils; Mice, Inbred C57BL; Mice, Inbred CBA; Liver; Female
PubMed: 38942904
DOI: 10.1038/s41598-024-65281-0 -
Scientific Reports Jun 2024Eukaryotic cells can synthesize formyl-methionine (fMet)-containing proteins not only in mitochondria but also in the cytosol to some extent. Our previous study revealed...
Eukaryotic cells can synthesize formyl-methionine (fMet)-containing proteins not only in mitochondria but also in the cytosol to some extent. Our previous study revealed substantial upregulation of N-terminal (Nt)-fMet-containing proteins in the cytosol of SW480 colorectal cancer cells. However, the functional and pathophysiological implications remain unclear. Here, we demonstrated that removal of the Nt-formyl moiety of Nt-fMet-containing proteins (via expressing Escherichia coli PDF peptide deformylase) resulted in a dramatic increase in the proliferation of SW480 colorectal cancer cells. This proliferation coincided with the acquisition of cancer stem cell features, including reduced cell size, enhanced self-renewal capacity, and elevated levels of the cancer stem cell surface marker CD24 and pluripotent transcription factor SOX2. Furthermore, deformylation of Nt-fMet-containing proteins promoted the tumorigenicity of SW480 colorectal cancer cells in an in vivo xenograft mouse model. Taken together, these findings suggest that cytosolic deformylation has a tumor-enhancing effect, highlighting its therapeutic potential for cancer treatment.
Topics: Humans; Neoplastic Stem Cells; Animals; Cytosol; Mice; Cell Line, Tumor; Cell Proliferation; Amidohydrolases; Colorectal Neoplasms; CD24 Antigen; SOXB1 Transcription Factors; Disease Progression; Methionine
PubMed: 38942903
DOI: 10.1038/s41598-024-65701-1 -
Scientific Reports Jun 2024Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the...
Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.
Topics: Humans; Male; Female; Plaque, Atherosclerotic; Aged; Middle Aged; Biomarkers; Amyloid beta-Peptides; Carotid Arteries; Ultrasonography; Carotid Intima-Media Thickness; Carotid Artery Diseases; Endarterectomy, Carotid
PubMed: 38942831
DOI: 10.1038/s41598-024-64906-8 -
Scientific Reports Jun 2024Remote sensing has been increasingly used in precision agriculture. Buoyed by the developments in the miniaturization of sensors and platforms, contemporary remote...
Remote sensing has been increasingly used in precision agriculture. Buoyed by the developments in the miniaturization of sensors and platforms, contemporary remote sensing offers data at resolutions finer enough to respond to within-farm variations. LiDAR point cloud, offers features amenable to modelling structural parameters of crops. Early prediction of crop growth parameters helps farmers and other stakeholders dynamically manage farming activities. The objective of this work is the development and application of a deep learning framework to predict plant-level crop height and crown area at different growth stages for vegetable crops. LiDAR point clouds were acquired using a terrestrial laser scanner on five dates during the growth cycles of tomato, eggplant and cabbage on the experimental research farms of the University of Agricultural Sciences, Bengaluru, India. We implemented a hybrid deep learning framework combining distinct features of long-term short memory (LSTM) and Gated Recurrent Unit (GRU) for the predictions of plant height and crown area. The predictions are validated with reference ground truth measurements. These predictions were validated against ground truth measurements. The findings demonstrate that plant-level structural parameters can be predicted well ahead of crop growth stages with around 80% accuracy. Notably, the LSTM and the GRU models exhibited limitations in capturing variations in structural parameters. Conversely, the hybrid model offered significantly improved predictions, particularly for crown area, with error rates for height prediction ranging from 5 to 12%, with deviations exhibiting a more balanced distribution between overestimation and underestimation This approach effectively captured the inherent temporal growth pattern of the crops, highlighting the potential of deep learning for precision agriculture applications. However, the prediction quality is relatively low at the advanced growth stage, closer to the harvest. In contrast, the prediction quality is stable across the three different crops. The results indicate the presence of a robust relationship between the features of the LiDAR point cloud and the auto-feature map of the deep learning methods adapted for plant-level crop structural characterization. This approach effectively captured the inherent temporal growth pattern of the crops, highlighting the potential of deep learning for precision agriculture applications.
Topics: Deep Learning; Crops, Agricultural; Remote Sensing Technology; Vegetables; India; Agriculture; Solanum lycopersicum; Solanum melongena
PubMed: 38942825
DOI: 10.1038/s41598-024-65322-8 -
Scientific Reports Jun 2024Oxyberberine (OBB) is a significant natural compound, with excellent hepatoprotective properties. However, the poor water solubility of OBB hinders its release and...
Oxyberberine (OBB) is a significant natural compound, with excellent hepatoprotective properties. However, the poor water solubility of OBB hinders its release and absorption thus resulting in low bioavailability. To overcome these drawbacks of OBB, amorphous spray-dried powders (ASDs) of OBB were formulated. The dissolution, characterizations, and pharmacokinetics of OBB-ASDs formulation were investigated, and its hepatoprotective action was disquisitive in the D-GalN/LPS-induced acute liver injury (ALI) mouse model. The characterizations of OBB-ASDs indicated that the crystalline form of OBB active pharmaceutical ingredients (API) was changed into an amorphous form in OBB-ASDs. More importantly, OBB-ASDs showed a higher bioavailability than OBB API. In addition, OBB-ASDs treatment restored abnormal histopathological changes, improved liver functions, and relieved hepatic inflammatory mediators and oxidative stress in ALI mice. The spray drying techniques produced an amorphous form of OBB, which could significantly enhance the bioavailability and exhibit excellent hepatoprotective effects, indicating that the OBB-ASDs can exhibit further potential in hepatoprotective drug delivery systems. Our results provide guidance for improving the bioavailability and pharmacological activities of other compounds, especially insoluble natural compounds. Meanwhile, the successful development of OBB-ASDs could shed new light on the research process of poorly soluble medicine.
Topics: Animals; Toll-Like Receptor 4; Mice; Biological Availability; Berberine; Male; Solubility; Liver; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Oxidative Stress; Protective Agents; Lipopolysaccharides; Powders; Drug Delivery Systems
PubMed: 38942824
DOI: 10.1038/s41598-024-65190-2 -
Scientific Reports Jun 2024Plekhm2 is a protein regulating endosomal trafficking and lysosomal distribution. We recently linked a recessive inherited mutation in PLEKHM2 to a familial form of...
Plekhm2 is a protein regulating endosomal trafficking and lysosomal distribution. We recently linked a recessive inherited mutation in PLEKHM2 to a familial form of dilated cardiomyopathy and left ventricular non-compaction. These patients' primary fibroblasts exhibited abnormal lysosomal distribution and autophagy impairment. We therefore hypothesized that loss of PLEKHM2 impairs cardiac function via autophagy derangement. Here, we characterized the roles of Plekhm2 in the heart using global Plekhm2 knockout (PLK2-KO) mice and cultured cardiac cells. Compared to littermate controls (WT), young PLK2-KO mice exhibited no difference in heart function or autophagy markers but demonstrated higher basal AKT phosphorylation. Older PLK2-KO mice had body and heart growth retardation and increased LC3II protein levels. PLK2-KO mice were more vulnerable to fasting and, interestingly, impaired autophagy was noted in vitro, in Plekhm2-deficient cardiofibroblasts but not in cardiomyocytes. PLK2-KO hearts appeared to be less sensitive to pathological hypertrophy induced by angiotensin-II compared to WT. Our findings suggest a role of Plekhm2 in murine cardiac autophagy. Plekhm2 deficiency impaired autophagy in cardiofibroblasts, but the autophagy in cardiomyocytes is not critically dependent on Plekhm2. The absence of Plekhm2 in mice appears to promote compensatory mechanism(s) enabling the heart to manage angiotensin-II-induced stress without detrimental consequences.
Topics: Animals; Autophagy; Mice, Knockout; Fibroblasts; Mice; Myocytes, Cardiac; Protein Serine-Threonine Kinases; Myocardium; Cells, Cultured; Phosphorylation
PubMed: 38942823
DOI: 10.1038/s41598-024-65670-5 -
Scientific Reports Jun 2024Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1...
Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.
Topics: Humans; Male; Prostatic Neoplasms; TOR Serine-Threonine Kinases; Gene Expression Regulation, Neoplastic; Disease Progression; Signal Transduction; Cell Line, Tumor; CDC2 Protein Kinase; DNA Methylation; Promoter Regions, Genetic; Cell Proliferation; Down-Regulation; Prognosis; Cell Movement
PubMed: 38942821
DOI: 10.1038/s41598-024-66020-1