Snail Activity Research Articles

Predicting the immunomodulatory activity of probiotic lactic acid bacteria using supervised machine learning in a Cornu aspersum snail model

In the process of screening for probiotic strains, there are no clearly established bacterial phenotypic markers which could be used for the prediction of their in vivo mechanism of action. In this work, we demonstrate for the first time that Machine Learning (ML) methods can be used for accurately predicting the in vivo immunomodulatory activity of probiotic strains based on their cell surface phenotypic features using a snail host-microbe interaction model. A broad range of snail gut presumptive probiotics, including 240 new lactic acid bacterial strains (Lactobacillus, Leuconostoc, Lactococcus, and Enterococcus), were isolated and characterized based on their capacity to withstand snails' gastrointestinal defense barriers, such as the pedal mucus, gastric mucus, gastric juices, and acidic pH, in association with their cell surface hydrophobicity, autoaggregation, and biofilm formation ability. The implemented ML pipeline predicted with high accuracy (88 %) strains with a strong capacity to enhance chemotaxis and phagocytic activity of snails’ hemolymph cells, while also revealed bacterial autoaggregation and cell surface hydrophobicity as the most important parameters that significantly affect host immune responses. The results show that ML approaches may be useful to derive a predictive understanding of host-probiotic interactions, while also highlighted the use of snails as an efficient animal model for screening presumptive probiotic strains in the light of their interaction with cellular innate immune responses.

Littorina snails and Microphallus trematodes: Diverse consequences of the trematode-induced metabolic shifts.

The intricate relationships between parasites and hosts encompass a wide range of levels, from molecular interactions to population dynamics. Parasites influence not only the physiological processes in the host organism, but also the entire ecosystem, affecting mortality of individuals, the number of offspring through parasitic castration, and matter and energy cycles. Understanding the molecular mechanisms that govern host-parasite relationships and their impact on host physiology and environment remains challenging. In this study, we analyzed how infection with Microphallus trematodes affects the metabolome of two Littorina snail species inhabiting different intertidal zone shore levels. We applied non-targeted GC-MS-based metabolomics to analyze biochemical shifts induced by trematode infection in a host organism. We have identified changes in energy, amino acid, sugar, and lipid metabolism. In particular, we observed intensified amino acid catabolism and nitrogenous catabolites (glutamine, urea) production. These changes primarily correlated with infection and interspecies differences of the hosts rather than shore level. The changes detected in the host metabolism indicate that other aspects of life may have been affected, both within the host organism and at a supra-organismal level. Therefore, we explored changes in microbiota composition, deviations in the host molluscs behavior, and acetylcholinesterase activity (ACE, an enzyme involved in neuromuscular transmission) in relation to infection. Infected snails displayed changes in their microbiome composition. Decreased ACE activity in snails was associated with reduced mobility, but whether it is associated with trematode infection remains unclear. The authors suggest a connection between the identified biochemical changes and the deformation of the shell of molluscs, changes in their behavior, and the associated microbiome. The role of parasitic systems formed by microphallid trematodes and Littorina snails in the nitrogen cycle at the ecosystem level is also assumed.

Benzo[a]pyrene evokes epithelial-mesenchymal transition and pulmonary fibrosis through AhR-mediated Nrf2-p62 signaling

Benzo[a]pyrene (BaP) and its metabolic end product benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE), are known toxic environmental pollutants. This study aimed to analyze whether sub-chronic BPDE exposure initiated pulmonary fibrosis and the potential mechanisms. In this work, male C57BL6/J mice were exposed to BPDE by dynamic inhalation exposure for 8 weeks. Our results indicated that sub-chronic BPDE exposure evoked pulmonary fibrosis and epithelial-mesenchymal transition (EMT) in mice. Both in vivo and in vitro, BPDE exposure promoted nuclear translocation of Snail. Further experiments indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) and p62 were upregulated in BPDE-exposed alveolar epithelial cells. Moreover, Nrf2 siRNA transfection evidently attenuated BPDE-induced p62 upregulation. Besides, p62 shRNA inhibited BPDE-incurred Snail nuclear translocation and EMT. Mechanically, BPDE facilitated physical interaction between p62 and Snail in the nucleus, then repressed Snail protein degradation by p62-dependent autophagy-lysosome pathway, and finally upregulated transcriptional activity of Snail. Additionally, aryl hydrocarbon receptor (AhR) was activated in BPDE-treated alveolar epithelial cells. Dual-luciferase assay indicated activating AhR could bind to Nrf2 gene promoter. Moreover, pretreatment with CH223191 or α-naphthoflavone (α-NF), AhR antagonists, inhibited BPDE-activated Nrf2-p62 signaling, and alleviated BPDE-induced EMT and pulmonary fibrosis in mice. Taken together, AhR-mediated Nrf2-p62 signaling contributes to BaP-induced EMT and pulmonary fibrosis.

Helminth diversity and seasonality of Angiostrongylus cantonensis in hedgehogs from Mallorca.

Sentinel surveillance plays a critical role in monitoring pathogen circulation, assessing potential threats for species conservation, and evaluating the risk of spillover to human populations. This study provides a comprehensive exploration of helminth parasites in the Mediterranean-distributed hedgehog species Atelerix algirus in Mallorca, Balearic Islands. Using an integrated approach that combines necropsies and morphological and molecular identifications using the COI gene, we identified 11 helminth taxa in 135hedgehogs, representing half of those that died at the local wildlife hospital in Mallorca between 2019 and 2022. We report an overall A. cantonensis prevalence of 11.5% and confirm the first case of a subclinical neuroangiostrongyliasis infection in a wildlife host. Infection prevalences over the year revealed that only two species, the nematode A. cantonensis and the cestode Mathevotaenia sp., had a seasonal pattern, with most A. cantonensis cases occurring in autumn and, to a lesser extent, Mathevotaenia sp. cases in winter. This pattern is probably due to the higher abundance and greater activity of snails and slugs (intermediate hosts) during these seasons, with important implications for public health and strategies for prevention of neuroangiostrongyliasis. Other key findings include a high prevalence (88.1%) of the lungworm Crenosoma striatum and detection of the acanthocephalan Moniliformis saudi for the first time in A. algirus. We anticipate that our study will facilitate surveillance efforts and clarify species identities in future studies. Given the lethal effects of A. cantonensis infection in hedgehogs, further studies are needed to evaluate the threat this parasite represents to European wildlife.

Sphingolipid paracrine signaling impairs keratinocyte adhesion to promote melanoma invasion

Melanoma is the deadliest form of skin cancer due to its propensity to metastasize. It arises from melanocytes, which are attached to keratinocytes within the basal epidermis. Here, we hypothesize that, in addition to melanocyte-intrinsic modifications, dysregulation of keratinocyte functions could initiate early-stage melanoma cell invasion. We identified the lysolipid sphingosine 1-phosphate (S1P) as a tumor paracrine signal from melanoma cells that modifies the keratinocyte transcriptome and reduces their adhesive properties, leading to tumor invasion. Mechanistically, tumor cell-derived S1P reduced E-cadherin expression in keratinocytes via S1P receptor dependent Snail and Slug activation. All of these effects were blocked by S1P2/3 antagonists. Importantly, we showed that epidermal E-cadherin expression was inversely correlated with the expression of the S1P-producing enzyme in neighboring tumors and the Breslow thickness in patients with early-stage melanoma. These findings support the notion that E-cadherin loss in the epidermis initiates the metastatic cascade in melanoma.

Retraction Note: HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail

Retraction Note: HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail

Biochemical and histopathological responses of Biomphalaria alexandrina to RIPEX (plant growth regulator)

BackgroundPlant growth regulators are widely used in agriculture for increasing the growth and ripening of plants, but they endanger the aquatic ecosystem. The current study assessed the effect of sublethal exposure to RIPEX 48% EC concentrations (8 and 16 µL/L) on oxidative stress parameters, sex hormones, immune potential enzymes, differential hemocyte counts, and the histopathology of digestive glands and ovotestis in Biomphalaria alexandrina snails.ResultsRIPEX exposure caused an overall increase in Superoxide dismutase and Glutathione-S-Transferase activities in B. alexandrina. However, extreme RIPEX exposure inhibits SOD activity in snails. Malondialdehyde activity showed an increase in B. alexandrina exposed to both concentrations after all exposure periods. RIPEX also caused a significant increase in testosterone in snails exposed to 16 µL/L, it did, however, reduce hormone levels in snails exposed to 8 µL/L at 7 days. Regarding estradiol, there was a significant increase after 3 days of exposure to 16 µl/L and 7 days of exposure to 8 µL/L. RIPEX exposure also increased the activities of Myeloperoxidase and Adenosine deaminase enzymes in the digestive glands of snails. It increased the total hemocyte count of exposed snails as well as the number of granulocytes. Snail digestive glands and ovotestis showed pathological alterations after 7 days of RIPEX exposure.ConclusionsThese findings suggest that RIPEX is toxic to B. alexandrina and that this snail can be used as a bioindicator for environmental contamination with plant growth regulators.

Anti-EMT properties of ergothioneine attenuate lipopolysaccharide-induced oxidative stress-mediated acute lung injury via modulating TGF-β/smad/snail signaling pathway.

Acute lung injury (ALI) is a heterogeneous pulmonary illness that is fast developing and has a high fatality rate. The current investigation set out to interpret the convergence of oxidative stress, inflammatory cytokines, TNF-α, snail, vimentin, e-cadherin, and NF-kB activation in ALI pathology. The outcome of assays of oxidative stress, ELISA, and western blot showed the declined of CAT, SOD, GPx, IL-1β, TNF-α, and upregulation of TGF-β, smad2/3, smad4, NF-kB, snail, and vimentin, concurrently with downregulation of e-cadherin expression in lung tissues as well as BALF in LPS-injected rats. The photomicrographs of the lungs marked severe congestion, infiltration of cytokines, and thickening of the alveolar walls. Pretreatments of ergothioneine after LPS-induced ALI, inhibited EMT-induction by blocking TGF-β, smad2/3, smad4, snail, vimentin, NF-kB, and inflammatory cytokines, and increased the expression of E-cadherin and antioxidant levels in a dose-dependent manner. These events helped to restore lung histoarchitecture and reduce acute lung injury. The present findings suggest that ergothioneine at 100mg/kg is as effective as febuxostat (reference drug). The study concluded that ergothioneine may be replaced with febuxostat as a treatment option for ALI owing to its side effects after clinical trials for pharmaceutical purposes.

Multixenobiotic defence mechanism in native and exotic freshwater snails as a biomarker for land uses-changes

Human activities such as agriculture and urbanization generate a large number of substances like personal care products, pharmaceutical compounds, and pesticides, which often reach aquatic environments and represent a threat to biodiversity. Many organisms have developed different evolutionary strategies to remove pervasive substances from their bodies, allowing them to persist even in polluted environments, and one of these is the multixenobiotic resistance (MXR) mechanism associated with the expression of membrane proteins like P-glycoprotein (P-gp). Numerous chemical compounds with diverse functions and structures can modulate this mechanism, which can be employed as a pollution biomarker. We examined the MXR activity in two species of snails that inhabit Patagonian freshwaters. Functional assay measurements of MXR were conducted on the native Chilina dombeiana and the exotic Physella acuta in stream reaches affected by anthropogenic impacts. Results indicated that at agricultural sites, C. dombeiana snails had a more active MXR system than organisms sampled at reference and moderately disturbed urban sites, whereas P. acuta snails from agricultural and highly disturbed urban sites showed better detoxifying activity than organisms from reference sites. Only in exotic snails, part of this activity was due to the action of P-gp. The most important environmental variables explaining MXR activity were ammonium, nitrate and nitrite, phosphates, and electrical conductivity. These results show the promise of measuring MXR activity in native and exotic snails, as a biomarker in the environmental monitoring of Patagonian freshwaters.

Inhibition of alternative oxidase disrupts the development and oviposition of Biomphalaria glabrata snails

BackgroundBiomphalaria glabrata is one of the main intermediate hosts of Schistosoma mansoni, the most widespread species of Schistosoma. Our previous studies proved that alternative oxidase (AOX), the terminal oxidase in the mitochondrial respiratory chain, widely exists in several species of intermediate host snails of Schistosoma. Meanwhile, inhibition of AOX activity in Oncomelania hupensis snails could dramatically enhance the molluscicidal effect of niclosamide. As a hermaphroditic aquatic mollusc, the high fecundity and population density of B. glabrata increase the difficulty of snail control, which is one of the critical strategies for schistosomiasis elimination. The present study aimed to investigate the possible role of AOX in the development and fecundity of B. glabrata snail, which could be manipulated more manageable than other species of intermediate host snails of Schistosoma.MethodsThe dynamic expression of the AOX gene was investigated in different developmental stages and tissues of B. glabrata, with morphological change and oviposition behaviour observed from juvenile to adult snails. Furtherly, dsRNA-mediated knockdown of BgAOX mRNA and the AOX protein activity inhibiting was performed to investigate the effect of AOX on the development and oviposition of snails.ResultsThe BgAOX gene expression profile is highly related to the development from late juveniles to adults, especially to the reproductive system of snails, with a positive correlation of 0.975 between egg production and BgAOX relative expression in ovotestis of snails. The inhibition of BgAOX at the transcriptional level and AOX activity could efficiently inhibit snail growth. However, the interference at the BgAOX protein activity level led to more severe tissue damage and more significant inhibition of oviposition than at the transcriptional level. This inhibition of growth and oviposition decreased gradually with the increase in the snail size.ConclusionsThe inhibition of AOX could efficiently disrupt the development and oviposition of B. glabrata snails, and the intervention targeting AOX at the juvenile stage is more effective for snails. This investigation explored the role of AOX in the growth and development of snails. It would benefit snail control in the future by providing a potential target while using molluscicides more efficiently.Graphical abstract

Megakaryocyte-Derived IL-8 Acts as a Paracrine Factor for Prostate Cancer Aggressiveness through CXCR2 Activation and Antagonistic AR Downregulation.

Prostate cancer is the fifth leading cause of cancer-related mortality in men, primarily because of treatment resistance, recurrence, and metastasis. In the present study, we investigated the role of paracrine interleukin-8 (IL-8) in the antagonistic expression of IL-8 and androgen receptor (AR), and the contribution of IL-8 to prostate cancer aggressiveness. In hormone-responsive LNCaP cells that do not express IL-8, recombinant IL-8 treatment significantly increased expressions of IL-8, CXC chemokine receptor 2 (CXCR2), matrix metalloproteinase (MMP)-2/9, Snail, and vimentin. IL-8 treatment significantly decreased AR and E-cadherin expression. IL-8-induced gene expression changes were suppressed by navarixin, a CXCR1/2 inhibitor, and gallein, a Gβγ inhibitor. In PC-3 androgen-refractory prostate cancer cells, IL-8 knockdown reduced expressions of CXCR2, MMP-2/9, Snail, and vimentin, and increased AR and E-cadherin expressions at the mRNA and protein levels. Co-culture with MEG-01 human megakaryocytic cells secreting high levels of IL-8 induced gene expression changes in both LNCaP and PC-3 cells, similar to those induced by IL-8 treatment. The altered gene expressions were accompanied by significant activation of transcription factor Snail in LNCaP and PC-3 cells. Treatment with the CXCR blocker navarixin inhibited the invasion of PC-3 cells but not LNCaP cells. However, invasion induced by MEG-01 was inhibited by navarixin in both LNCaP and PC-3 cells. The collective findings demonstrate that IL-8 enhances CXCR2 expression, which antagonistically regulates AR expression. More importantly, through changes in IL-8/CXCR2-regulated gene expression, IL-8 induces antiandrogen therapy resistance and epithelial-mesenchymal transition in prostate cancer.

Substrate specificity of phenoloxidase-like activity in an ecoimmunological model speciesLymnaea stagnalis

ABSTRACTEcoimmunological research on molluscs and other invertebrates frequently quantifies phenoloxidase (PO) activity to estimate the strength of the immune function. PO enzymes form different families whose relative roles in oxidative reactions are typically unknown. Understanding this could allow enzyme-specific assays with higher accuracy than in commonly used nonspecific assays. We tested the contribution of different PO enzyme families to haemolymph PO-like activity in Lymnaea stagnalis snails using substrates specific to enzymes detected in L. stagnalis transcriptome data (p-phenylenediamine, specific to laccases; L-tyrosine, specific to tyrosinases) and compared the reactions to those with a nonspecific substrate (L-dopa). We found laccase-like but no tyrosinase-like activity. However, reactions with L-dopa were the strongest, possibly due to other oxidative enzymes in snail haemolymph. Laccase-like activity is common in molluscs, and we propose the use of enzyme-specific assays in future ecoimmunological studies of this taxon. The lack of tyrosinase-like activity in L. stagnalis contradicts earlier transcriptome data, which calls for investigating the expression of PO enzymes in L. stagnalis at the proteome level.

Previous stress causes a contrasting response to cadmium toxicity in the aquatic snail Potamopyrgus antipodarum: lethal and behavioral endpoints

In aquatic ecosystems, animals are often exposed to a combination of stressors, including both natural and anthropogenic factors. Combined stressors may have additive or interactive effects on animals, either magnifying or reducing the effects caused by each stressor alone. Therefore, standardized bioassays can lead to overestimations or underestimations of the risk of toxicants if natural stressors are not bear in mind. The inclusion of natural stress in laboratory bioassays may help to extrapolate the laboratory results to ecosystems. This study assesses the effects of successive exposure to two sources of stress (high water conductivity and cadmium toxicity) on the behavior and survival of the aquatic snail Potamopyrgus antipodarum (Tateidae, Mollusca). I conducted a bioassay consisting on exposure to high conductivity (5000 mg NaCl/L, 7 days), followed by exposure to cadmium (0.03, 0.125, and 0.25 mg Cd/L for 7 days) and by a post-exposure period (7 days). Mortality, inactivity, and the time to start activity of active animals were monitored in each animal. In general, cadmium lethality was higher in animals previously undergoing high conductivity than in non-stressed ones. Previously stressed animals showed longer time to start activity, with a noticeable effect at the two highest cadmium concentrations. Animals submitted to the two highest cadmium concentration both, stressed and non-stressed, showed a moderate recovery during the post-exposure period. It is concluded that previous stress caused a worsening of the cadmium toxicity on the aquatic snail Potamopyrgus antipodarum, which is especially noticeable for mortality. However, there was no interactive effect between cadmium and conductivity on snail activity, which may be indicative of recovery after cadmium exposure regardless the previous stress suffered by the snails.

Pirfenidone Attenuates the EMT Process and the Secretion of VEGF in TGF-β2-Induced ARPE-19 Cells via Inhibiting the Activation of the NF-κB/Snail Signaling Pathway.

Pirfenidone (PFD), an antifibrotic drug, has various beneficial functions such as antioxidant, antifibrotic, and anti-inflammatory effects. This study aimed to explore the molecular mechanisms underlying how PFD modulates retinal pigment epithelial (RPE) cells involved in neovascularization and subretinal fibrosis. ARPE-19 cell lines were treated with transforming growth factor-beta 2 (TGF-β2) alone or in combination with PFD. RPE cell viability, as a consequence of PFD use, was determined by the CCK-8 assay. Cell migration was assessed by the wound closure assay and quantified by the Image J software. Protein expression of the following markers was measured by the western blot analysis: an epithelial cell marker and E-cadherin; mesenchymal cell markers, fibronectin, matrix metalloprotein-9 (MMP-9), and alpha-smooth muscle actin (α-SMA); a fibrotic marker and connective tissue growth factor (CTGF); an angiogenesis marker and vascular endothelial growth factor (VEGF); NF-κB/Snail. The mRNA levels of fibronectin and α-SMA were determined by quantitative real-time PCR. VEGF was quantitatively measured by the enzyme-linked immunosorbent assay. The cell viability assay revealed that PFD had no significant cytotoxic effect on RPE cells at concentrations of less than 1 mg/mL. The cell scratch assay showed that TGF-β2 stimulation significantly improved the migration of RPE cells and that PFD attenuated this effect. PFD significantly inhibited the TGF-β2-induced protein expression of E-cadherin and increased the TGF-β2-induced protein expression of fibronectin, MMP-9, α-SMA, CTGF, and VEGF in ARPE-19 cells. The mRNA expression of fibronectin and α-SMA was inhibited by PFD in TGF-β2-inducedARPE-19 cells. Additionally, the increased intracellular and supernatant expression of VEGF protein was suppressed by PFD. Mechanistically, RPE cells treated with PFD + TGF-β2 exhibited a decrease in phosphorylation of the NF-κB P65 subunit and activation of Snail, compared with the RPE cells treated with TGF-β2 alone. PFD ameliorated TGF-β2-induced neovascularization and fibrosis by suppressing the NF-κB/Snail signaling pathway. Therefore, PFD may be a potential drug in the treatment of age-related macular degeneration.

Snail meat consumption in Buea-Cameroon: exposures to foodborne pathogens through social practices assessed in 2019 and 2021

BackgroundSnail meat is an important source of nutrition in Cameroon, but the food safety risks are poorly understood. We characterized public health risks from snail meat consumption as a social system in Cameroon, by examining local snail practices that expose snail meat handlers and consumers to foodborne pathogens.MethodsWe used exploratory qualitative approaches, that is, lived experience, face-to-face in-depth interviews, participant observation and a focus group, to explore fifteen key informants’ routines and lived experiences, and perceptions of two health officials on the food safety practices around snail meat consumption in Cameroon. This information was organized and interpreted using Soft Systems Methodology and Social Practice Theory, which permitted a systemic appreciation of local practices.ResultsWe distinguished five kinds of actors (snail vendors, market sellers, street vendors, street eaters and home consumers), who performed seven successive practices (picking, selling, cracking, washing, cooking, hawking and eating). We then identified three worldviews about snails: family support or to reduce poverty, a source of nutrition and a food choice (taste, preference). Our findings revealed participants’ competences were based on childhood learning and ‘inborn’ experiences, and materials used in snail activities reflected participants’ parentage and ‘state of poverty’. Although most interviewees highlighted ‘unhygienic conditions’ when explaining snail picking locations, participants believed washing and cooking should kill all contaminants.ConclusionSeveral opportunities for human exposures to foodborne pathogens including snail picking in domestic wastes and sewage, the selling of unpackaged live snails, improper snail meat washing and hawking in loosely closed buckets, were apparent from our analysis. These findings suggest fruitful opportunities aimed at improving health outcomes among African snail meat handlers and consumers.

Suppression of androgen receptor signaling induces prostate cancer migration via activation of the CCL20-CCR6 axis.

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.

BAIAP2L1 accelerates breast cancer progression and chemoresistance by activating AKT signaling through binding with ribosomal protein L3.

BAI1-associated protein 2-like 1 (BAIAP2L1), also known as insulin receptor tyrosine kinase substrate, modulates the insulin network; however, its function in breast cancer has not been explored. Immunohistochemical analysis of 140 breast cancer specimens (77 triple-negative and 63 nontriple-negative cases) indicated that BAIAP2L1 expression was higher in breast cancer tissues (56/140, 40%) than in normal breast tissues (28.3%, 15/53; p< 0.001). BAIAP2L1 expression in breast cancer was correlated with triple-negative breast cancer (p=0.0013), advanced TNM stage (p=0.001), lymph node metastasis (p=0.001), and poor patient prognosis (p=0.001). BAIAP2L1 overexpression could accelerate breast cancer proliferation, invasion, and stemness in vivo and in vitro, possibly through the activation of AKT, Snail, and cyclin D1. Treatment with the AKT inhibitor LY294002 reduced the effects of BAIAP2L1 overexpression on breast cancer cells. BAIAP2L1 may bind to the AA202-288 of ribosomal protein L3 (RPL3) within its SRC homology 3 (SH3) domain, the loss of which may abolish the transduction of the AKT signaling pathway by promoting the degradation of PIK3CA. Moreover, BAIAP2L1 overexpression may induce chemotherapy resistance, with BAIAP2L1 expression being higher in patients with advanced Miller grades than those with lower grades. Our results indicated that BAIAP2L1 promotes breast cancer progression through the AKT signaling pathway by interacting with RPL3 through its SH3 domain.

LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway

BackgroundEpithelial-to-mesenchymal transition (EMT) is a critical event contributing to more aggressive phenotypes in cancer cells. EMT is frequently activated in radiation-targeted cells during the course of radiotherapy, which often endows cancers with acquired radioresistance. However, the upstream molecules driving the signaling pathways of radiation-induced EMT have not been fully delineated.MethodsIn this study, RNA-seq-based transcriptome analysis was performed to identify the early responsive genes of HeLa cells to γ-ray irradiation. EMT-associated genes were knocked down by siRNA technology or overexpressed in HeLa cells and A549 cells, and the resulting changes in phenotypes of EMT and radiosensitivity were assessed using qPCR and Western blotting analyses, migration assays, colony-forming ability and apoptosis of flow cytometer assays. ResultsThrough RNA-seq-based transcriptome analysis, we found that LPAR5 is downregulated in the early response of HeLa cells to γ-ray irradiation. Radiation-induced alterations in LPAR5 expression were further revealed to be a bidirectional dynamic process in HeLa and A549 cells, i.e., the early downregulating phase at 2 ~ 4 h and the late upregulating phase at 24 h post-irradiation. Overexpression of LPAR5 prompts EMT programing and migration of cancer cells. Moreover, increased expression of LPAR5 is significantly associated with IR-induced EMT and confers radioresistance to cancer cells. Knockdown of LPAR5 suppressed IR-induced EMT by attenuating the activation of ERK signaling and downstream Snail, MMP1, and MMP9 expression.ConclusionsLPAR5 is an important upstream regulator of IR-induced EMT that modulates the ERK/Snail pathway. This study provides further insights into understanding the mechanism of radiation-induced EMT and identifies promising targets for improving the effectiveness of cancer radiation therapy.

Population Dynamics of Abundant Three Terrestrial Snail Species in Horticultural Fields at Beheira and Giza Governorate, Egypt.

&lt;b&gt;Background and Objective:&lt;/b&gt; Studying the population dynamic of the invasive terrestrial snails as agricultural pests, is essential for designing pest control program to reduce the economic losses to commercial field crops, vegetables and fruits. The population dynamic had been estimated for the three terrestrial snails &lt;i&gt;Theba pisana &lt;/i&gt;(Müller, 1774) (Helicidae), &lt;i&gt;Eobania vermiculata &lt;/i&gt;(Müller, 1774) (Helicidae) and &lt;i&gt;Monacha obstructa&lt;/i&gt; (Pfeiffer, 1842) (Hygromiidae) on orange, apple and mango trees in horticultural fields in two locations. These locations are Nobaria City, Beheira Governorate and Mansouria Village, Giza Governorate. This study carried out during the two consecutive activity seasons September, 2018/August, 2019 and September, 2019/August, 2020. &lt;b&gt;Materials and Methods:&lt;/b&gt; The population dynamic, incidence and infestation level of terrestrial snails had been recorded on economic host plants such as fruit trees and other field crops and vegetables. The correlations between climatic factors and the population density of land snails were interpreted by statistical analysis for the two seasons. &lt;b&gt;Results:&lt;/b&gt; The population density of terrestrial snails increased gradually after winter to reach its maximum density during spring, while the lowest density was recorded in August. The incidence and infestation level of terrestrial snails varied according to the host plant, climatic factors and locality. &lt;i&gt;Eobania vermiculata&lt;/i&gt; were the dominant land snail species in Beheira, while &lt;i&gt;Monacha obstructa&lt;/i&gt; infested the majority of the examined fruit trees in Giza. &lt;b&gt;Conclusion:&lt;/b&gt; Determining the activity and inactivity periods of land snails through the two seasons and their population dynamic will assist in designing effective control management program to decrease the number of pest and the economic losses of agricultural products.

Chlorogenic Acid Inhibition of Esophageal Squamous Cell Carcinoma Metastasis via EGFR/p-Akt/Snail Signaling Pathways

Chlorogenic acid (CGA) is a polyphenol compound found in a variety of foods, including coffee, tea, cherries, and apples. It has been found by a number of studies to affect the viability of human cancer cells. No study has investigated its effect on esophageal squamous cell carcinoma (ESCC) metastasis or the molecular mechanism underlying its effect on this disease. We first used the Taiwanese ESCC cell line CE81T/VGH to create CE81T-M4 cells. Treatment of higher motility cells with chlorogenic acid for 24 h led to inhibition of cell migration and invasion as shown by scratch migration and transwell assays. Western blotting showed that chlorogenic acid halted the activation of EGFR/p-Akt/Snail pathway and suppressed the expression of MMP-2 and MMP-9. Knockdown of either EGFR or Akt inhibited Snail, MMP2, and MMP9 activity as well as cell migration and invasion. Chlorogenic acid inhibited cancer cell motility via the EGFR/p-Akt/Snail pathway and could potentially be used to develop an antimetastatic agent for ESCC in the future.