Mechanisms Of Invasion Research Articles

P12.14.B HIGHLY INVASIVE GLIOMA CELLS MOTILITY MEASUREMENTS ON A VARIETY OF EXTRACELLULAR MATRIX PROTEINS

Abstract BACKGROUND Glioblastoma multiforme (GBM) is a heterogeneous highly invasive malignant brain tumor. The extracellular matrix (ECM) produced by tumor microenvironment plays an important role in the regulation of cell motility and invasion into surrounding healthy tissue. In this research we determined the effect of various ECM proteins on the motility of primary tumor cells. MATERIAL AND METHODS Primary tumor cells were isolated from biopsy material obtained during GBM surgical removal. Cultivation of the piece of tumor (0.5 mm3) was carried out in the form of an 3D explant model at 37°C in 5% CO2-incubator. After several months, cells migrated from the tumor spontaneously formed spheroids. To assess the rate of cell migration, spheroids were seeded on 24-well plate coated with poly-L-lysine, fibrinogen, collagen type I, and Matrigel. After 3 days, the field of view in the well (n=9) was microphotographed every 15 min for 56 hours, after which the tracks of cells outside the spheroids were manually marked (n=50) on the obtained images. The average and maximum speeds were calculated, as well as the straightness of the track (the ratio of the Euclidean distance to the track length). The Mean square displacement (MSD) was plotted against time for each protein studied in comparison with random walk simulation calculated for the equal track parameters (number of steps, mean and sd) on correspondent protein. RESULTS Live-cell imaging of the patient-derived cells revealed the heterogeneous population of actively moving cells outside the spheroids. The following results of measuring cell motility were obtained (mean ± sd): (1) Mean speed on poly-L-lysine 4.3 ± 2.5 μm/h; on fibrinogen 11.1 ± 5.7 μm/h; on collagen type I 8.8 ± 5.1 μm/h; on Matrigel 9.7 ± 3.6 μm/h. (2) Max speed on poly-L-lysine 63.8 ± 30.1 μm/h; on fibrinogen 90.0 ± 38.9 μm/h; on collagen type I 96.1 ± 42.1 μm/h; on Matrigel 84.1 ± 34.1 μm/h. (3) Straightness on poly-L-lysine 0.24 ± 0.14 μm/h; on fibrinogen 0.18 ± 0.11 μm/h; on collagen type I 0.14 ± 0.09 μm/h; on Matrigel 0.20 ± 0.12 μm/h. MSD analysis showed the greatest contribution of random walk in the motility of cells on collagen type I, the smallest - on Matrigel. CONCLUSION Proteins of ECM affect not only the speed of cell movement, but also the tortuosity of their tracks. Further studies will clarify the mechanisms of GBM invasion depending on the composition of the ECM.

Identification and comprehensive analysis of super-enhancer related genes involved in epithelial-to-mesenchymal transition in lung adenocarcinoma.

Lung adenocarcinoma is a disease with a high mortality rate, and its mechanism is still unclear. Super-enhancers play an important role in gene expression and also affect the occurrence and development of lung adenocarcinoma, so more and more people pay attention to them. In order to explore the influence of super-enhancer related genes on tumor development, we identified super-enhancer regulated genes related to Epithelial-to-mesenchymal transition (EMT). By analyzing the single-cell sequencing data and the TCGA database of lung adenocarcinoma, we suggest that the up-regulation of TMSB10 in lung adenocarcinoma and its association with poor prognosis may be due to the regulation of super-enhancers during tumor cell metastasis. Using the TCGA lung adenocarcinoma data set, the samples were divided into TMSB10 high-expression group and low-expression group, and it was found that there were significant differences in immune infiltration between the high-expression group and the low-expression group. We parted 513 samples into eight TMSB10-related molecular subtypes using differentially expressed genes of high and low TMSB10 expression groups. We concentrated on four molecular subtypes with the most significant clusters, each with its own characteristics in terms of Immune cell infiltration, prognosis, or pathological stages. In order to predict the four molecular subtypes, we established a prediction model using random forest, and the external test results showed that the prediction accuracy of the model was 0.87. This study may provide potential help for the study of the mechanism of metastasis and invasion of lung adenocarcinoma cells and personalized treatment of lung adenocarcinoma.

Progesterone receptor membrane component 2 is critical for human placental extravillous trophoblast invasion.

Proper extravillous trophoblast invasion is essential for normal placentation and pregnancy. However, the molecular mechanisms by which cytotrophoblasts differentiate into extravillous trophoblast are unclear. We discovered that in the first-trimester placenta, progesterone receptor membrane component 2 was highly expressed in syncytiotrophoblast but significantly lower in extravillous trophoblast and cytotrophoblasts, indicating a divergent role for progesterone receptor membrane component 2 in trophoblast functions. We aim to examine the role of progesterone receptor membrane component 2 in extravillous trophoblasts invasion mediated by both intracellular and extracellular signals. Progesterone receptor membrane component 2 knockdown and overexpression cells were established in HTR8/SVneo cells, a first-trimester extravillous trophoblast-derived cell model, by transfection with small-interfering RNA or progesterone receptor membrane component 2 plasmids, respectively. Progesterone receptor membrane component 2 knockdown led to cellular morphological changes , enhanced trophoblast proliferation,invasion, and promoted tube formation. These effects were mediated by the activation of hypoxia-inducible factor 1alpha and an increased expression of vascular endothelial growth factor A. The culture supernatant collected from progesterone receptor membrane component 2 knockdown cells did not significantly affect extravillous trophoblast invasion compared to the controls, indicating that extracellular signaling did not robustly regulate extravillous trophoblast invasion in this study. In conclusion, attenuation of progesterone receptor membrane component 2 plays a role in placentation by promoting cell proliferation, invasion, and angiogenesis in extravillous trophoblasts via activation of hypoxia-inducible factor 1 alpha signaling. We thus identified a new function of progesterone receptor membrane component 2 and provide insights on understanding the mechanisms of trophoblast invasion.

The Impact and Invasive Mechanisms of Pueraria montana var. lobata, One of the World's Worst Alien Species.

Pueraria montana var. lobata is native to East Asia, and was introduced to many countries due to its potential for multiple uses. This species escaped under the management conditions soon after its introduction, and became a harmful weed species. This species has been listed in the top 100 of the world's worst invasive alien species. P. montana stands expand quickly and threaten the native flora and fauna including microbiota. This species affects the concentration of carbon and nitrogen in soil and aquatic environments, and increases the amount of pollutants in the local atmosphere. Its infestation also causes serious economic losses on forestry and agriculture. Its characteristics of fast growth, thick canopy structure, enormous vegetative reproduction, and adaptative ability to the various environmental conditions may contribute to the invasiveness and naturalization of this species. The characteristics of P. montana regarding their defense functions against their natural enemies and pathogens, and allelopathy may also contribute to the invasiveness of this species. Potential allelochemicals such as xanthoxins, p-coumaric acid, caffeic acid, methyl caffeate and daidzein, and two isoflavones with anti-virus activity were identified in this species. In addition, fewer herbivore insects were found in the introduced ranges. These characteristics of P. montana may be involved in the invasive mechanisms of the species. This is the first review article focusing on the invasive mechanisms of this species.

Invasive Wedelia trilobata Performs Better Than Its Native Congener in Various Forms of Phosphorous in Different Growth Stages.

At present, many hypotheses have been proposed to explain the mechanism of alien plants' successful invasion; the resource fluctuations hypothesis indicates that nutrient availability is a main abiotic factor driving the invasion of alien plants. Higher phosphorus utilization and absorption efficiency might be one of the important reasons for alien plants successful invasion. Wedelia trilobata, one of the notorious invasive weeds in China, possesses a strong ability to continue their development under infertile habitats. In this study, firstly, W. trilobata and its native congener, W. chinensis, were grown in various phosphorus forms to test their absorption efficiency of phosphorus. Secondly, the different responses of W. trilobata and W. chinensis to the insoluble phosphorus in three growth stages (at 30, 60, and 150 days cultivation) were also tested. The results showed that the growth rate, root morphology, and phosphorus absorption efficiency of W. trilobata under various insoluble, organic, or low phosphorus conditions were significantly higher than that of W. chinensis. During the short-term cultivation period (30 d), the growth of W. trilobata under insoluble and low phosphorus treatments had no significant difference, and the growth of W. trilobata in insoluble phosphorus treatment also had no significant effect in long-term cultivation (60 and 150 d). However, the growth of W. chinensis in each period under the conditions of insoluble and low phosphorus was significantly inhibited throughout these three growth stages. Therefore, invasive W. trilobata had a higher phosphorus utilization efficiency than its native congener. This study could explain how invasive W. trilobata performs under nutrient-poor habitats, while also providing favorable evidence for the resource fluctuations hypothesis.

A pilot in vivo study: potential ovarian cancer therapeutic by placental extracellular vesicles.

The biological links between cancer and pregnancy are of interest due to parallel proliferative, immunosuppressive, and invasive mechanisms between tumour and placental cells. However, the proliferation and invasion of placental cells are strictly regulated. The understanding of this regulation is largely unknown. Placental extracellular vesicles (EVs) may play an important role in this regulation, as placental EVs are known to contribute to maternal adaptation, including adaptation of the vascular and immune systems. We have previously reported that placental EVs significantly inhibited ovarian cancer cell proliferation by delaying the progression of the cell cycle. We therefore performed this pilot in vivo study to investigate whether placental EVs can also inhibit ovarian tumour growth in a SKOV-3 human tumour xenograft model. A single intraperitoneal injection of placental EVs at 15 days post tumour implantation, significantly inhibited the growth of the tumours in our in vivo model. Signs of cellular necrosis were observed in the ovarian tumour tissues, but not in other organs collected from mice that had been treated with placental EVs. Expression of receptor-interacting kinase 1 (RIPK1) and mixed linkage kinase domain-like (MLKL), which are mediators of necroptosis were not observed in our xenografted tumors. However, extensive infiltration of CD169+ macrophages and NK cells in ovarian tumour tissues collected from placental micro-EVs treated mice were observed. We demonstrate here that inhibition of ovarian tumour growth in our xenograft model by placental EVs involves cellular necrosis and infiltration of CD169+ macrophages and NK cells into the tumour tissues.

FGF13A interacts with NPM1 and UBF and inhibits the invasion of bladder cancer cells

Bladder cancer (BC) invasion is a critical factor that impacts the prognosis and quality of life of patients. However, the underlying mechanisms of BC invasion is far from clear. Fibroblast growth factor 13 (FGF13), a non-secretory FGF, has been found to be ectopically expressed in various tumors and implicated in tumor development, but its potential association to BC has not been investigated. Here, we reported that the expression of FGF13A, one nucleolar isoform of FGF13, was downregulated in BC patients and negatively associated with tumor invasion. Additionally, we demonstrated that overexpression of FGF13A could inhibit the migration and invasion of BC 5637 and T24 cells. We also confirmed the localization of FGF13A in the nucleolus and its interaction with nucleoproteins NPM1 and UBP. Subsequently, we identified that the N-terminal region of FGF13A was essential for its nucleolus location and interaction with NPM1. Furthermore, we found that FGF13A inhibited the generation of nascent ribosomal RNA and suppressed the migration and invasion of BC cells through its N-terminal region. Our research establishes, for the first time, a correlation between the expression of FGF13A and the onset and progression of BC. This provides novel insights into the role of FGF13A in the development of BC.

Assessing the mechanisms and impacts of shrub invasion in forests: A meta‐analysis

Abstract The encroachment of invasive shrubs in forest understories can have detrimental effects on native plant recruitment. As a result, removal of invasive species is a common practice although long‐lasting success is rare. In order to effectively conserve and manage invaded forests, it is crucial to understand the mechanisms that drive shrub invasion, that is, high propagule pressure, low native resistance and exploitation of empty niches. To gain a deeper understanding of the invasion process in forest ecosystems we conducted a meta‐analysis of the work done in this topic. We collected data on invasive species and native community performance, and on the abiotic conditions of forest understories under low and high levels of shrub invasion. We analysed data from 124 articles that yielded 377 unique observations. Our results revealed that while invader performance did not vary by the mechanism of invasion, the impact on the native community was significantly detrimental when invasion occurred via low biotic resistance, and only marginally significant via propagule pressure. Invasive species performance was associated with increases in light availability, but not with other resources (soil water or nutrients). When assessing impact on native performance as a function of invasive performance, results were again only significant under the low biotic resistance mechanism. Lastly, impacts were stronger when invasion took place by a single invader. Synthesis and applications. Taken together, these results suggest that restoration efforts should focus on (i) increasing the presence of strong native competitors or functionally diverse native communities, (ii) decreasing sources of invasive shrub propagules while keeping the canopies closed when invasion occurs via high propagule pressure, (iii) avoiding management techniques that degrade or diminish canopy cover and (iv) prioritizing management of forest understories dominated by particularly impactful invasive shrubs.

Upregulated CXCL8 in placenta accreta spectruma regulates the migration and invasion of HTR-8/SVneo cells.

Placenta accreta spectrum (PAS) is mainly characterized by excessive invasion of the uterine muscle layer accompanied by a large number of foreign blood vessels, leading to severe bleeding during and after delivery. However, the mechanism of excessive invasion of nutrient cells in placenta accreta is currently unclear. We performed RNA sequencing of 6 PAS patients and 4 control donors, coupled with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The mRNA and protein expression of C-X-C motif ligand 8 (CXCL8) in the placental tissue was measured by qRT‒PCR, immunohistochemical staining and Western blotting. HTR-8/SVneo human villous trophoblast Neo cells were used for in vitro investigation of cell migration and invasion as well as the expression level of CXCL8. A total of 1120 differentially expressed mRNAs were identified in PAS patients. Moreover, GO and KEGG analyses indicated that the differentially expressed mRNAs were most closely associated with immune system processes, biological adhesion and Wnt signaling pathway. The CXCL8 mRNA and protein levels in PAS tissue were significantly higher than those in normal placental tissue. Forced overexpression of CXCL8 significantly increased the migration and invasion of HTR-8/SVneo cells, accompanied by the upregulation of matrix metalloproteinase-2 and matrix metalloproteinase-9 and the downregulation of E-cadherin, which was reversed by knockdown of CXCL8. CXCL8 was highly expressed in PAS, and knockdown of CXCL8 suppressed the migration and invasion of HTR-8/SVneo cells, suggesting its potential as a diagnostic and therapeutic target for PAS.

Plant invasion and fragmentation indirectly and contrastingly affect native plants and grassland arthropods

Plant invasion and habitat fragmentation have a detrimental effect on biodiversity in nearly all types of ecosystems. We compared the direct and indirect effects of the invasion of the common milkweed (Asclepias syriaca) on biodiversity patterns in different-sized Hungarian forest-steppe fragments. We assessed vegetation structure, measured temperature and soil moisture, and studied organisms with different ecological roles in invaded and non-invaded sites of fragments: plants, bees, butterflies, flower-visiting wasps, flies, true bugs, and spiders. Temperature and soil moisture were lower in invaded than in non-invaded area. Milkweed had a positive effect on plant species richness and flower abundance. In contrast, we mainly found indirect effects of invasion on arthropods through alteration of physical habitat characteristics and food resources. Pollinators were positively affected by native flowers, thus, milkweed indirectly supported pollinators. Similarly, we found higher species richness of herbivores in invaded sites than control sites, as species richness of true bugs also increased with increasing plant species richness. Predators were positively affected by complex vegetation structure, higher soil moisture and lower temperature. Furthermore, increasing fragment size had a strong negative effect on spider species richness of non-invaded sites, but no effect in invaded sites. Especially, grassland specialist spiders were more sensitive to fragment size than generalists, whereas generalist spider species rather profited from invasion. Although milkweed invades natural areas, we did not identify strong negative effects of its presence on the diversity of the grassland biota. However, the supportive effect of milkweed on a few generalist species homogenises the communities. The rate of invasion might increase with increasing fragmentation, therefore we recommend eliminating invasive plants from small habitat fragments to preserve the native biota. Focusing also on generalist species and revealing the indirect effects of invasions are essential for understanding the invasion mechanisms and would support restoration efforts.

A disintegrin and metalloproteinase 22 activates integrin β1 through its disintegrin domain to promote the progression of pituitary adenoma.

Approximately 35% of pituitary adenoma (PA) display an aggressive profile, resulting in low surgical total resection rates, high recurrence rates, and worse prognosis. However, the molecular mechanism of PA invasion remains poorly understood. Although "a disintegrin and metalloproteinases" (ADAMs) are associated with the progression of many tumors, there are no reports on ADAM22 in PA. PA transcriptomics databases and clinical specimens were used to analyze the expression of ADAM22. PA cell lines overexpressing wild-type ADAM22, the point mutation ADAM22, the mutated ADAM22 without disintegrin domain, and knocking down ADAM22 were generated. Cell proliferation/invasion assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, mass spectrometry, Reverse transcription-quantitative real-time PCR, phos-tag SDS-PAGE, and Western blot were performed for function and mechanism research. Nude mice xenograft models and rat prolactinoma orthotopic models were used to validate in vitro findings. ADAM22 was significantly overexpressed in PA and could promote the proliferation, migration, and invasion of PA cells. ADAM22 interacted with integrin β1 (ITGB1) and activated FAK/PI3K and FAK/ERK signaling pathways through its disintegrin domain to promote PA progression. ADAM22 was phosphorylated by PKA and recruited 14-3-3, thereby delaying its degradation. ITGB1-targeted inhibitor (anti-itgb1) exerted antitumor effects and synergistic effects in combination with somatostatin analogs or dopamine agonists in treating PA. ADAM22 was upregulated in PA and was able to promote PA proliferation, migration, and invasion by activating ITGB1 signaling. PKA may regulate the degradation of ADAM22 through post-transcriptional modification levels. ITGB1 may be a potential therapeutic target for PA.

Mucinous Colorectal Carcinoma Arising in Nonulcerated Villous Adenoma (MAVA): A Distinct Pathologic Entity

Among 209 surgical specimens of resectable colorectal adenocarcinomas, nine mucinous carcinomas arising in nonulcerated villous adenoma (MA VA) were identified. They showed infUtration in the colorectal muscillaris própria or through it. However, their morphology was similar to the so-called pseudocarcinomatous submucous foci of villous adenomas. Only one of these tumors had lymph-node metastasis. We suggest that the mechanism of invasion of the colorectal wall in MAMA is diferent from that of the common adenocarcinoma, not implying an authentic carcinomatous transformation at cellular level.

Effect of saline–alkaline stresses on the interspecific competition between Aegilops tauschii and Triticum aestivum

Soil salinization has produced severe consequences on global agricultural production and ecological environment. Based on the features of saline soils in China, through mixed NaCl, NaHCO3, Na2SO4, and Na2CO3 at varying ratios to simulate the salinity–alkalinity stress and conducted a controlled pot experiment using De Wit replacement method. The effects of salinity–alkalinity stress on the growth of Aegilops tauschii and its competition with wheat were explored to provide a reference for the study of invasion mechanism of A. tauschii. The result showed that, the salinity–alkalinity stress inhibited the growth and development of both the species, which was reflected in plant height, leaf area and total biomass indicators. Secondly, the tolerance of both plant species to salinity–alkalinity stress was improved by increasing the superoxide dismutase (SOD) activity and the proline content. However, as the salinity–alkalinity stress was exacerbated, the relative conductivity and thiobarbituric acid (TBARS) content increased significantly in both the species. As suggested by the level of increase in SOD activity, proline content, relative conductivity, and TBARS content, A. tauschii was more tolerant to the salinity–alkalinity stress than wheat. Finally, it can be seen from the value of the competition balance index, A. tauschii was still more competitive than wheat even under salinity–alkalinity stress. In summary, A. tauschii was more tolerant of the salinity–alkalinity stress than wheat through the favorable adjustment of morphology, biomass allocation pattern, and physiological features, which is expected to increase its invasion damage to wheat.

ORFV entry into host cells via clathrin-mediated endocytosis and macropinocytosis

Orf virus (ORFV), also known as infectious pustular virus, leads to an acute contagious zoonotic infectious disease. ORFV can directly contact and infect epithelial cells of skin and mucosa, causing damage to tissue cells. So far, the pathway of ORFV entry into cells is unclear. Therefore, finding the internalization pathway of ORFV will help to elucidate the cellular and molecular mechanisms of ORFV infection and invasion, which in turn will provide a certain reference for the prevention and treatment of ORFV. In the present study, chemical inhibitors were used to analyze the mechanism of ORFV entry into target cells. The results showed that the inhibitor of clathrin-mediated endocytosis could inhibit ORFV entry into cells. However, the inhibitor of caveolae-mediated endocytosis cannot inhibit ORFV entry into cells. In addition, inhibition of macropinocytosis pathway also significantly reduced ORFV internalization. Furthermore, the inhibitors of acidification and dynamin also prevented ORFV entry. However, results demonstrated that inhibitors inhibited ORFV entry but did not inhibit ORFV binding. Notably, extracellular trypsin promoted ORFV entry into cells directly, even when the endocytic pathway was inhibited. In conclusion, ORFV enters into its target cells by clathrin-mediated endocytosis and macropinocytosis, while caveolae-dependent endocytosis has little effects on this process. In addition, the entry into target cells by ORFV required an acid environment and the effect of dynamin. Meanwhile, we emphasize that broad-spectrum antiviral inhibitors and extracellular enzyme inhibitors are likely to be effective strategies for the prevention and treatment of ORFV infection.

Role of long pentraxin PTX3 in cancer.

Cancer has become a leading cause of death and disease burden worldwide, closely related to rapid socioeconomic development. However, the fundamental reason is the lack of comprehensive understanding of the mechanism of cancer, accurate identification of preclinical cancer, and effective treatment of the disease. Therefore, it is particularly urgent to study specific mechanisms of cancer and develop effective prediction and treatment methods. Long Pentraxin PTX3 is a soluble pattern recognition molecule produced by various cells in inflammatory sites, which plays a role as a promoter or suppressor of cancer in multiple tumors through participating in innate immune response, neovascularization, energy metabolism, invasion, and metastasis mechanisms. Based on this, this article mainly reviews the role of PTX3 in various cancers.

The dispersal of dinoflagellate cyst caused by international ships under repair conditions: a potential invasion risk to the Yangtze River Estuary, China.

The foreign dinoflagellate cysts in ships' ballast water tank sediments (BWTS) can be viable for a long time under hostile storage conditions. It is crucial to understand the detailed mechanisms of harmful biological invasions in estuary ecosystems. To study the relationship between the abundance of dinoflagellate cysts and environmental factors, cyst assemblages were analyzed in 7 sediment samples, collected from one international commercial ship that arrived in Shanghai in August 2020. Twenty-three dinoflagellate cyst taxa were identified in 5 groups, including autotrophic (9) and heterotrophic (14) species. Distribution of dinoflagellate cysts in the different ballast water tanks is heterogeneous. Dinoflagellate cysts in BWTS of the repaired ship were dominated by Scrippsiella acuminata, Protoperidinium leonis, Protoperidinium oblongum, Lingulodinium polyedra, Alexandrium tamarense/A. catenella, Protoperidinium pentagonum, and Protoperidinium subinerme. The abundance of the dinoflagellate cysts in each tank ranged from 80.69 to 330.85 cysts g-1 DS (dry sediment). Multivariate statistical analyses revealed that the variation in cysts from different tanks had positive correlations with total nitrogen (TN), total phosphorus (TP), and pH and negative correlations with total organic carbon (TOC) except for sample TK5. For germination of dinoflagellate cysts in BWTS, 12 species were germinated in 40days and cysts of potentially toxic dinoflagellate species were more abundant than those of non-toxic species. Results show that potentially viable and harmful/toxic dinoflagellate cysts are present in BWTS of ships arriving in Shanghai, China. Consequently, knowledge obtained in this study can be valuable for further managing of potential biological invasion of the Yangtze River Estuary.

Proteomic profiles of male and female Caligus rogercresseyi: first approach to assess differential protein expression

Caligidosis is a disease that affects salmonids in sea and estuaries of the Chilean coast, with a negative impact in the aquaculture activity, producing great economic damage to salmon farming. This parasitic disease is caused by the marine ectoparasite Caligus rogercresseyi, commonly known as “Caligus”. In recent years, our understanding about the biology of Caligus has been increased by the use of “omics” tools such as genomics and transcriptomics. Indeed, progress in these areas revolutionize our understanding about the physiology of this parasite, in particular, the metabolic process and the invasive mechanisms associated with infestation. However, the knowledge of the changes in protein expression levels during the different stages of the life cycle or under stress conditions of an organism, as well as the differences between sexes, have a very interesting role in the development of specific and effective pharmacological tools against this parasite. Nevertheless, the proteomic information about this parasite is insufficient. In this study, we evaluated differential expression of proteins between males and females C. rogercresseyi not exposed to antiparasitic treatments, using a tandem mass tags (TMT)-based proteomic approach, which allows the simultaneous identification and quantification of protein expression profiles from multiple samples in a single LC-MS/MS analysis. Here, we report the first advance of the proteomic analysis from male and female C. rogercresseyi. By TMT we detect 1666 proteins, of which 1307 were expressed in both males and females. However, within this group of proteins, the differential expression between males and females was detected in 688 proteins. Furthermore, between the proteins expressed exclusively in each sex, 148 proteins were detected exclusively males and 211 proteins in females. Several of the proteins described here have previously been associated with changes in their transcriptional expression levels in response to different antiparasitic drugs. The sex-biased protein expression described in this work makes sense with the different antiparasitic sensitivities observed between males and females of C. rogercresseyi.This work is the first mass identification analysis of proteins in C. rogercresseyi in which we definitively established the existence of a sex-biased protein expression.

Bacterial Membrane Vesicles: Physiological Roles, Infection Immunology, and Applications.

Bacterial or fungal membrane vesicles, traditionally considered as microbial metabolic wastes, are secreted mainly from the outer membrane or cell membrane of microorganisms. However, recent studies have shown that these vesicles play essential roles in direct or indirect communications among microorganisms and between microorganisms and hosts. This review aims to provide an updated understanding of the physiological functions and emerging applications of bacterial membrane vesicles, with a focus on their biogenesis, mechanisms of adsorption and invasion into host cells, immune stimulatory effects, and roles in the much-concerned problem of bacterial resistance. Additionally, the potential applications of these vesicles as biomarkers, vaccine candidates, and drug delivery platforms are discussed.

Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to a poor overall prognosis. Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape. The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets. In this review, we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC, summarize the potential signaling pathways modulating the neuronal-cancer interaction, and discuss the current and future therapeutic possibilities for this condition.

FBXO28 promotes proliferation, invasion, and metastasis of pancreatic cancer cells through regulation of SMARCC2 ubiquitination.

The E3 ligase F-box only protein 28 (FBXO28) belongs to the F-box family of proteins that play a critical role in tumor development. However, the potential function of FBXO28 in pancreatic cancer (PC) and its molecular mechanism remain unclear. In this study, we examined FBXO28 expression in PC and its biological role and explored the mechanism of FBXO28-mediated proliferation, invasion, and metastasis of PC cells. Compared with paracancerous tissues and human normal pancreatic ductal epithelial cells, FBXO28 was highly expressed in PC tissues and cell lines. High expression of FBXO28 was negatively correlated with the survival prognosis of patients with PC. Functional assays indicated that FBXO28 promoted PC cell proliferation, invasion, and metastasis in vitro and in vivo. Furthermore, immunoprecipitation-mass spectrometry was used to identify SMARCC2 as the target of FBXO28; upregulation of SMARCC2 can reverse the effect of overexpression of FBXO28 on promoting the proliferation, invasion, and metastasis of PC cells. Mechanistically, FBXO28 inhibited SMARCC2 expression in post-translation by increasing SMARCC2 ubiquitination and protein degradation. In conclusion, FBXO28 has a potential role in PC, possibly promoting PC progression through SMARCC2 ubiquitination. Thus, FBXO28 might be a potential treatment target in PC.