COL6A1 Inhibits the Malignant Development of Bladder Cancer by Regulating FBN1.

Bladder cancer (BLCA) is a prevalent malignancy worldwide with a high recurrence rate. Collagen Type VI Alpha 1 (COL6A1) plays a key role in several cancer types. In this study, we aimed to explore the role of COL6A1 in BLCA. COL6A1 expression in BLCA was determined using The Cancer Genome Atlas database and real-time quantitative polymerase chain reaction (RT-qPCR). Counting Kit-8, wound-healing, and transwell assays were used to assess the effect of COL6A1 on T24 and 5637 cells. Apoptosis in BLCA cell lines was explored using western blotting and flow cytometry. Co-immunoprecipitation was performed to determine interactions between proteins. The role of COL6A1 in tumor growth in nude mice was evaluated by hematoxylin-eosin, immunohistochemical, and terminal deoxynucleotidyl transferase dUTP Nick-End Labeling. In BLCA, COL6A1 expression was downregulated. Moreover, the COL6A1 overexpression suppressed the viability, migration, and invasion, while promoting apoptosis of BLCA cell lines, with increased Caspase-3, Bax, and p53, and decreased Bcl-2. Conversely, silencing of COL6A1 promoted proliferation, migration, and invasion, while inhibiting apoptosis in BLCA cell lines. In vivo, COL6A1 inhibits tumor growth and progression. Fibrillin-1 (FBN1) was positively correlated with COL6A1 expression. COL6A1 could bind to FBN1 in BLCA cell lines. The expression of FBN1 in BLCA cell lines decreased after COL6A1 silencing, whereas COL6A1 overexpression upregulated FBN1 expression. COL6A1 was downregulated and exerted an inhibitory effect on the development of BLCA, and its expression was positively correlated with the expression of FBN1.

Roles of small peptides encoded by non-coding RNAs in tumor invasion and migration.

Non-coding RNAs (ncRNAs), which are usually considered not to encode proteins, are widely involved in important activities including signal transduction and cell proliferation. However, recent studies have shown that small peptides encoded by ncRNAs (SPENs) have important roles in the development of malignant tumors. Some SPENs participate in the regulation of skeleton reorganization, intercellular adhesion, signaling and other processes of tumor cells, with effects on the invasive and migratory abilities of the cells. Therefore, SPENs have potential applications as therapeutic targets and biomarkers of malignant tumors. Invasion and migration of malignant tumor cells are the main reasons for poor prognosis of cancer patients and represent the most challenging aspects of treatment of malignant tumors. Currently, the main treatments for tumors include surgery, radiotherapy, targeted drug therapy. Surgery, however, is reserved for early stages of cancer and carries risks and costs. Radiotherapy and targeted therapy have serious side effects. This review describes the mechanisms of SPENs and their roles in tumor invasion and migration, with the aim of providing new targets for tumor diagnosis and treatment.

Assessing microvascular invasion in HBV-related hepatocellular carcinoma: an online interactive nomogram integrating inflammatory markers, radiomics, and convolutional neural networks.

Objective: The early recurrence of hepatocellular carcinoma (HCC) correlates with decreased overall survival. Microvascular invasion (MVI) stands out as a prominent hazard influencing post-resection survival status and metastasis in patients with HBV-related HCC. The study focused on developing a web-based nomogram for preoperative prediction of MVI in HBV-HCC. Materials and methods: 173 HBV-HCC patients from 2017 to 2022 with complete preoperative clinical data and Gadopentetate dimeglumine-enhanced magnetic resonance images were randomly divided into two groups for the purpose of model training and validation, using a ratio of 7:3. MRI signatures were extracted by pyradiomics and the deep neural network, 3D ResNet. Clinical factors, blood-cell-inflammation markers, and MRI signatures selected by LASSO were incorporated into the predictive nomogram. The evaluation of the predictive accuracy involved assessing the area under the receiver operating characteristic (ROC) curve (AUC), the concordance index (C-index), along with analyses of calibration and decision curves. Results: Inflammation marker, neutrophil-to-lymphocyte ratio (NLR), was positively correlated with independent MRI radiomics risk factors for MVI. The performance of prediction model combined serum AFP, AST, NLR, 15 radiomics features and 7 deep features was better than clinical and radiomics models. The combined model achieved C-index values of 0.926 and 0.917, with AUCs of 0.911 and 0.907, respectively. Conclusion: NLR showed a positive correlation with MRI radiomics and deep learning features. The nomogram, incorporating NLR and MRI features, accurately predicted individualized MVI risk preoperatively.

Recent advancements in understanding of biological role of homeobox C9 in human cancers.

Homeobox (HOX) C9, a member of the HOX family, is an important transcription factor, and it plays a significant role in various biological processes. This family of genes is highly valued for their essential roles in establishing and maintaining the body axis during embryonic development and adult tissues. Further, HOXC9 plays a central role in neuronal differentiation, angiogenesis, and adipose distribution, which are essential for the development of the nervous system, maturation of tissues and organs, and maintenance of energy balance and metabolic health. Recent research has found that abnormal HOXC9 expression is closely associated with the development and progression of various tumor types. The HOXC9 expression level can be an indicator of tumor prognosis. Therefore, elucidating the association between HOXC9 expression and its regulatory mechanisms and tumorigenesis can provide novel insights on the diagnosis and treatment of patients with cancer.

Ecological Effects of the Huge Invasive Species Removal Project in Coastal China.

Saltmarsh wetlands are recognized as some of the most ecologically valuable yet vulnerable ecosystems globally. However, since the 1970s, saltmarsh wetlands in coastal China have been seriously threatened by the invasive Spartina alterniflora. Although the Chinese government has initiated a nationwide S. alterniflora removal project, the potential benefits and risks of this project remain unknown. Here, we focus on the Yangtze River Estuary Saltmarsh Wetland (YRESW) and simulate its future ecosystem structure, function, and quality under three scenarios based on remote sensing and field investigation data. The simulation scenarios include the absence of a removal project, natural regeneration postproject (NRP), and planted restoration postproject. The results show that the removal project will reverse the escalating invasion trend of S. alterniflora in the YRESW. Compared to the baseline year of 2022, there is a remarkable increase in ecosystem structure (composition: +107%, configuration: +27%) and ecosystem quality (+10.5%) under the NRP scenario. Although blue carbon storage sharply decreases under both scenarios involving project implementation, planted restoration can restore YRESW's carbon sequestration capacity to 0.19 Tg C per year, achieving 87% of the carbon storage present before the project. This study underscores the necessity of comprehensive and detailed risk assessments in ecological projects, particularly when dominant species are involved. Our findings hold significant implications for stabilizing coastal wetland ecosystems and promoting sustainable development in coastal areas.

Preliminary investigation on the mechanism of baicalein regulating the effects of Nischarin on invasion and apoptosis of human breast cancer cells MCF-7 through Wnt3α/ß-catenin pathway.

BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related mortality in women. Here, we investigate the anti-tumor effects of baicalein on human BC cells (MCF-7 cells) and explore if it regulates the Nischarin protein via Wnt3α/ß-catenin signaling pathway. METHODS: We employed Wnt3α and DKK-1 to activate and inhibit the Wnt/ß-catenin signaling pathway, respectively. We used CCK-8 cell viability, flow cytometry apoptosis, wound-healing and transwell migration/invasion assays. Further, using western blotting and real-time quantitative PCR (q-PCR) we analyzed expression levels of Nischarin, MMP-9, Wnt/ß-catenin pathway (ß-catenin, Axin 1), and apoptotic pathway (Bax, Bcl-2) proteins and their mRNAs. RESULTS: We found that baicalein inhibits MCF-7 cell viability and promotes apoptosis (evidenced by increased Bax and decreased Bcl-2 expressions) in a concentration-dependent manner. It also inhibits TPA-induced migration and invasion, and downregulates MMP-9 expression. Baicalein reverses the increase in cell viability caused by Wnt3α-induced Wnt/ß-catenin pathway activation. Conversely, baicalein counteracts the increase in apoptosis caused by DKK-1 mediated inhibition of the Wnt/ß-catenin pathway. Additionally, baicalein upregulates Nischarin expression via modulating the Wnt/ß-catenin pathway as indicated by the antagonistic effects of Wnt3α and DKK-1 on this effect of baicalein. CONCLUSION: Baicalein exerts anti-tumor effects on MCF-7 cells through the Wnt3α/ß-catenin signaling pathway, and promotes apoptosis and inhibits migration and invasion. The upregulation of Nischarin by baicalein further suggests a potential therapeutic target for BC treatment.

Ecosystem links: Anthropogenic activities, environmental variables, and macrophytes structure snail preferences in man-made waterbodies.

Freshwater snails act as obligate intermediate hosts for trematode parasites that cause trematodiases threatening public and veterinary health, and biodiversity conservation. While interest in snail control for trematodiases has re-emerged, their ecology remains poorly understood. We examined the relationship between ecosystem indicators - such as environmental variables, macroinvertebrates, macrophytes, and land use - and their correlation with snail abundance, diversity, and infection prevalence in 19 man-made ponds in eastern Zimbabwe. In total, 926 freshwater snails from 10 species were collected, with 547 individuals belonging to five schistosome-competent species: Bulinus tropicus, Bulinus truncatus, Bulinus globosus, Bulinus forskalii, and Biomphalaria pfeifferi. The remaining 379 snails comprised Radix natalensis, Gyraulus sp., and the exotic invasive species Melanoides tuberculata, Pseudosuccinea columella, and Physella acuta. Six cercarial types - mammalian schistosomes, avian schistosomes, longifurcate pharyngeates, echinostomes, amphistomes, and xiphidiocercariae - were isolated from 104 out of 926 snails (11.2 %). PCR revealed a significantly higher infection rate, with 70.2 % of snails testing positive for trematodes. Snail taxon diversity and infection rate significantly varied across land use types, with the lowest values observed in the commercial tobacco farm section, highlighting the potential adverse effects of agriculture on biodiversity. Ponds with extensive Lagarosiphon major (oxygen weed) coverage appeared to facilitate the presence and abundance of P. acuta and P. columella. Schistosome-competent snails such as B. truncatus and B. tropicus seemed to favor shallow water depths and more eutrophic sites characterized by high levels of nitrates, phytoplankton biomass, turbidity, and phycocyanin. These ponds were predominantly associated with the emergent macrophyte Cladium mariscus, revealing a potential association with important intermediate snail hosts. In conclusion, our study emphasizes the complex interplay among environmental factors, macrophyte composition, land use, and the abundance, diversity, and infection prevalence of freshwater snails, offering insights into potential strategies for targeted snail control and disease management in man-made waterbodies.

Quantifying vulnerability to plant invasion across global ecosystems.

The widely referenced "tens rule" in invasion ecology suggests that approximately 10% of established, non-native species will become invasive. However, the accuracy of this estimate has been questioned, as the original analysis focused on small groups of plant species in Great Britain and Australia. Using a novel database of 9501 established plants and 2924 invasive plants, we provide a comprehensive evaluation of the tens rule and the first empirical analysis of how invasion rates vary across spatial scales, islands/mainlands, and climate zones. We found that invasion rates (the percentage of established species with negative impacts) are highly variable across the globe. Well-sampled environments (those with at least 2000 total non-native species recorded) had invasion rates that ranged from 7.2% to 33.8%. Invasion rates were strongly scale-dependent, averaging 17% at the country scale and 25% at the continental scale. We found significantly higher invasion rates on islands when compared with mainlands, regardless of scale. Tropical ecosystems are often considered to be resistant to invasion; however, our results showed significantly higher invasion rates on both tropical islands and mainlands, suggesting unexpectedly high vulnerability of these species-rich ecosystems. We conclude that the tens rule is a poor general estimate of invasion rates for plants, as calculated invasion rates vary widely and are frequently much higher than 10%. Most locations would be better served by using invasion rates that vary based on the recipient environment. Our updated estimates of invasion rates should be highly relevant for invasive species management strategies, including weed risk assessments, which can be adjusted to identify more species as high-risk in areas where invasion rates are higher. Assuming that 10% of established species will become invasive is likely to substantially underestimate invasion rates in most geographies.

Synergistic effect of bazedoxifene and abemaciclib co­treatment in triple­negative breast cancer cells in vitro.

Triple-negative breast cancer (TNBC) is an aggressive disease with the capability of metastasizing quickly. However, treatment options for patients with TNBC still remain limited. CDK4/6 inhibitors have been approved by the U.S. Food and Drug Administration and are administered for the treatment of hormone receptor-positive breast cancer subtypes, but not yet for TNBC. Although pre-clinical research is being conducted on their efficacy in treating TNBC, acquired resistance to CDK4/6 inhibitors is now a growing clinical problem. One of the identified resistance mechanisms is through the IL-6/STAT3 signaling pathway. In the present study, the CDK4/6 inhibitor, abemaciclib, was tested in combination with the IL-6 inhibitor, bazedoxifene, on human (SUM159 and MDA-MB-231) and murine (4T1) TNBC cell lines. Both abemaciclib and bazedoxifene monotherapies inhibited cell cycle progression and cell viability, migration and invasion, and induced apoptosis; however, the combination treatment exerted a greater effect than either monotherapy. These findings support the concept of CDK4/6 and IL-6 dual inhibition as a novel targeted therapy against TNBC.

Evaluating fish foraging behaviour on non-indigenous Asparagopsis taxiformis using a remote video foraging system.

The proliferation of pest and invasive marine macroalgae threatens coastal ecosystems, with biotic interactions, including direct effects such as grazing and indirect effects such as the trophic cascades, where one species indirectly affects another through its interactions with a third species, play a critical role in determining the resistance of local communities to these invasions. This study examines the foraging behaviour and preference of native fish communities toward native (Halopteris scoparia, Sargassum vulgare) and non-indigenous (Asparagopsis taxiformis) macroalgae using the Remote Video Foraging System (RVFS). Fifty-four weedpops were deployed across three locations to present these macroalgae, while associated epifaunal assemblages were also collected. Video analysis revealed that four common fish species displayed preference towards native macroalgae, possibly due to by the presence of zoobenthos rather than herbivory. This observation suggests that these fish species identified the macroalgae as a habitat that harboured their preferred food items. In contrast, A. taxiformis was consistently avoided, suggesting limited integration into the local food web. Site-specific variations in fish-macroalgae interactions and epifaunal diversity highlighted the complexity of these dynamics. This study contributes to understanding of the ecological implications of invasive macroalgae and supports the use of RVFS as a tool for assessing local biotic resistance against non-indigenous species in coastal ecosystems globally.