PGRN inhibits CD8+T cell recruitment and promotes breast cancer progression by up-regulating ICAM-1 on TAM.

BACKGROUND: Tumor microenvironment actually reduces antitumor effect against the immune attack by exclusion of CD8+T cells. Progranulin (PGRN) is a multifunctional growth factor with significant pathological effects in multiple tumors; however, its role in immunity evasion of breast cancer (BCa) is not completely understood. METHODS: We depleted GRN (PGRN gene) genetically in mice or specifically in PY8119 murine BCa cell line, and mouse models of orthotopic or subcutaneous transplantation were used. Chimeric mice-deficient of PGRN (Grn-/-) in bone marrow (BM) compartment was also generated. Association of PGRN expression with chemokine production or BCa development was investigated by histological and immunological assays. RESULTS: We found PGRN was involved in exhaustion of cytotoxic CD8+T cell in BCa with the increasing expressions of M2 markers and intercellular cell adhesion molecule-1 (ICAM-1) on macrophages. Specifically, ablation of PGRN in PY8119 cells reduced tumor burden, accompanied by the infiltrating of cytotoxic CD8+T cells into tumor nests. Moreover, our result revealed that blockade of PD-1 in PGRN-depleted tumors exhibited better antitumor effect in vivo and significantly decreased tumor burden. CONCLUSION: These findings suggest that inhibition of PGRN may act as a potential immune-therapeutic strategy by recovering infiltration of CD8+T cell in BCa tissue and thereby enhancing the response to anti-PD-1 therapy.

Target recycle initiated entropy driven assembly strategy for sensitive, enzyme-free, and portable miRNA detection.

MicroRNA (miRNA) is a pivotal biomarker in the diagnosis of various cancers, including bladder cancer (BCa). Despite their significance, the low abundance of miRNA presents a substantial challenge for sensitive and reliable detection. We introduce an innovative, highly sensitive assay for miRNA expression quantification that is both enzyme-free and portable. This method leverages the synergy of target recycling and entropy-driven assembly (EDA) for enhanced sensitivity and specificity. The proposed method possesses several advantages, including i) dual signal amplification through target recycling and EDA, which significantly boosts sensitivity with a lower limit of detection of 2.54 fM; ii) elimination of enzyme requirements, resulting in a cost-effective and stable signal amplification process; and iii) utilization of a personal glucose meter (PGM) for signal recording, rendering the method portable and adaptable to diverse settings. In summary, this PGM-based approach holds promising potential for clinical molecular diagnostics, offering a practical and efficient solution for miRNA analysis in cancer detection.

Adherence to a healthy sleep pattern and risk of urologic cancers: A large prospective cohort study.

OBJECTIVE: A variety of unhealthy sleep behaviors have been shown to be associated with an increased risk of urologic cancers. However, little is known about the association between the overall sleep patterns and urologic cancers. To prospectively investigate the associations between a healthy sleep pattern and the risks of urologic cancers, including bladder cancer (BCa) and renal cell carcinoma (RCC). METHODS: In this prospective cohort study, 377,144 participants free of cancer at baseline were recruited from the UK Biobank. Data on sleep behaviors were collected through questionnaires at recruitment. The incident urologic cancer cases were determined through linkage to national cancer and death registries. We established a healthy sleep score according to five sleep traits (sleep duration, chronotype, insomnia, snoring, and daytime sleepiness). Cox proportional hazard regression models were used to calculate the adjusted hazard ratios and 95% confidence intervals to assess the relationship between the healthy sleep score and the risk of urologic cancers. RESULTS: During a median of ≥9 years of follow-up, we identified 1986 incident urologic cancer cases, including 1272 BCa cases and 706 RCC cases. Compared with the participants with a poor sleep pattern (score of 0-2), the multivariable-adjusted hazard ratio and 95% confidence interval were 0.85 (0.75 to 0.96) for urologic cancers, 0.80 (0.68 to 0.93) for BCa, and 0.91 (0.74, 1.12) for RCC, respectively, for those with the healthier sleep pattern (score of 4-5). CONCLUSION: Our results indicate that a healthy sleep pattern is associated with lower risks of urologic cancers.

Biocontrol Agents of Fusarium Head Blight in Wheat: A Meta-Analytic Approach to Elucidate Their Strengths and Weaknesses.

The use of biocontrol agents (BCAs) coping with fungal pathogens causing Fusarium head blight (FHB) is a compelling strategy for disease management, but a better elucidation of their effectiveness is crucial. Meta-analysis is the analysis of the results of multiple studies, which is typically performed to synthesize evidence from many possible sources in a formal probabilistic manner. This meta-analytic study, including 30 pathometric, biometric, physiochemical, genetic, and mycotoxin response variables reported in 56 studies, evidences the BCA effects on FHB in wheat. The effectiveness of BCAs of FHB in wheat in terms of pathogen abundance and disease reductions, biomass and yield conservation, and mycotoxin prevention/control was confirmed. BCAs showed higher efficacy (i) in studies published more recently; (ii) under controlled conditions; (iii) in high susceptible wheat cultivars; (iv) when Fusarium inoculation and BCA treatment did not occur directly on the plant (i.e., at the seed and kernel levels) in terms of disease development and mycotoxin control, and vice versa in terms of biomass conservation; (v) if Fusarium inoculation and BCA treatment occurred by spraying spikes in terms of yield; (vi) at 15 to 21 days post Fusarium inoculation or BCA treatment; and (vii) if they were filamentous fungi. However, BCAs overall were less efficacious than conventional agrochemicals, especially in terms of pathogen abundance and FHB reductions, as well as of mycotoxin prevention/control, although inconsistencies were reported among the investigated moderator variables. This study also highlights the complexity of reaching a good balance among BCA effects, and the need for further research.

Determination of N-Acetyl-L-cysteine Ethyl Ester (NACET) by Sequential Injection Analysis.

New sequential injection analysis (SIA) methods with optical sensing for the determination of N-acetyl-L-cysteine ethyl ester (NACET) have been developed and optimized. NACET is a potential drug and antioxidant with advantageous pharmacokinetics. The methods involve the reduction of Cu(II) in its complexes with neocuproine (NCN), bicinchoninic acid (BCA), and bathocuproine disulfonic acid (BCS) to the corresponding chromophoric Cu(I) complexes by the analyte. The absorbance of the Cu(I) complexes with NCN, BCA, and BCS was measured at their maximum absorbance wavelengths of 458, 562, and 483 nm, respectively. The sensing manifold parameters and experimental conditions were optimized for each of the Cu(II) complexes used. Under optimal conditions, the corresponding linear calibration ranges, limits of detection, and sampling rates were 8.0 × 10-6-2.0 × 10-4 mol L-1, 5.5 × 10-6 mol L-1, and 60 h-1 for NCN; 6.0 × 10-6-1.0 × 10-4 mol L-1, 5.2 × 10-6 mol L-1, and 60 h-1 for BCA; and 4.0 × 10-6-1.0 × 10-4 mol L-1, 2.6 × 10-6 mol L-1, and 78 h-1 for BCS. The Cu(II)-BCS complex was found to be best performing in terms of sensitivity and sampling rate. Usual excipients in pharmaceutical preparations did not interfere with NACET analysis.

Bifunctional Chiral Agent Enables One-pot Spontaneous Deracemization of Racemic Compounds.

A novel one-pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α-diphenyl-2-pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2R,3R)-enantiomer and (2S,3S)-enantiomer in solution, achieving a one-pot spontaneous deracemization. This strategy was also successfully extended to the deracemization of three other racemic compound drugs: (R,S)-carprofen, (R,S)-indoprofen, and (R,S)-indobufen. The one-pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization-induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy.

MassSpecPreppy-An end-to-end solution for automated protein concentration determination and flexible sample digestion for proteomics applications.

In proteomics, fast, efficient, and highly reproducible sample preparation is of utmost importance, particularly in view of fast scanning mass spectrometers enabling analyses of large sample series. To address this need, we have developed the web application MassSpecPreppy that operates on the open science OT-2 liquid handling robot from Opentrons. This platform can prepare up to 96 samples at once, performing tasks like BCA protein concentration determination, sample digestion with normalization, reduction/alkylation and peptide elution into vials or loading specified peptide amounts onto Evotips in an automated and flexible manner. The performance of the developed workflows using MassSpecPreppy was compared with standard manual sample preparation workflows. The BCA assay experiments revealed an average recovery of 101.3% (SD: ± 7.82%) for the MassSpecPreppy workflow, while the manual workflow had a recovery of 96.3% (SD: ± 9.73%). The species mix used in the evaluation experiments showed that 94.5% of protein groups for OT-2 digestion and 95% for manual digestion passed the significance thresholds with comparable peptide level coefficient of variations. These results demonstrate that MassSpecPreppy is a versatile and scalable platform for automated sample preparation, producing injection-ready samples for proteomics research.

The dynamic changes of monocytes and cytokines during wound healing post-burn injury.

BACKGROUND: Burn injury is a sudden and traumatic injury that affects a large part of the population worldwide, who are placed at high risk of developing hypertrophic scars (HTS). HTS are a fibrotic scar resulting in painful contracted and raised scarring, affecting mobility in joints and work life, as well as cosmetically. The aim of this research was to enhance our understanding of the systematic response of monocytes and cytokines in wound healing after burn injury, in order to develop novel approaches to prevention and treatment of HTS. METHODS: Twenty-seven burn patients and thirteen healthy individuals were recruited in this study. Burn patients were stratified by burn total body surface area (TBSA). Peripheral blood samples were taken post-burn injury. Serum and peripheral blood mononuclear cells (PBMCs) were separated from the blood samples. This research investigated cytokines IL-6, IL-8, IL1RA, IL-10, and chemokine pathways SDF-1/CXCR4, MCP-1/CCR2, RANTES/CCR5 during the wound healing process in burn patients with varying severity of injuries by using enzyme-linked immunosorbent assays. PBMCs were stained for monocytes and the chemokine receptors by flow cytometry. Statistical analysis was done by one-way ANOVA with a Tukey correction, and regression analysis was performed using Pearson's Correlation analysis. RESULTS: The CD14+ CD16- monocyte subpopulation is larger in patients who developed HTS at 4-7 days. The CD14+ CD16+ monocyte subpopulation is smaller in the first week of injury, where it is similar after 8 days. Burn injury increased CXCR4, CCR2, and CCR5 expressions in CD14+ CD16+ monocytes. Increases in MCP-1 at 0-3 days after burn injury was positively correlated with burn severity. IL-6, IL-8, RANTES, and MCP-1 significantly increased with increasing burn severity. CONCLUSIONS: Monocytes and their chemokine receptors, as well as systemic levels of cytokines in wound healing of burn patients and scar development will require ongoing assessment to enhance our understanding of the abnormal wound healing after burn injury.

An innovative model based on N7-methylguanosine-related lncRNAs for forecasting prognosis and tumor immune landscape in bladder cancer.

BACKGROUND: As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. METHODS: We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan-Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. RESULTS: We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. CONCLUSION: The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.

Silver nanoparticles induced with aqueous black carpenter ant extract selectively inhibit the growth of Pseudomonas aeruginosa.

Aqueous black carpenter ant extract (ABCAE) was used to synthesize silver nanoparticles (AgNPs). The ABCAE was rich in water-soluble compounds such as hydrophilic polypeptides that behaved as both reducing and stabilizing agents for generating AgNPs from Ag+ ion precursors. The diameter of the observed AgNPs was mostly in the range of 20-60 nm. The AgNPs were tested as an antibacterial agent for the growth inhibition of two pathogenic bacteria (Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 27661) and one common bacteria (Escherichia coli K12 ATCC 10798). Disk diffusion test showed that the AgNPs selectively inhibited the growth of P. aeruginosa but not for the other two species, suggesting the potential application of the green-chemically synthesized AgNPs as a selective antibacterial agent without harming other beneficial bacteria.

Management of scalp arteriovenous malformations: a rising trend towards percutaneous direct puncture embolization technique-our experience.

BACKGROUND: Scalp arteriovenous malformations (AVMs), or cirsoid aneurysms of the scalp, usually present with troublesome symptoms and cosmetic disfigurement. Endovascular/percutaneous embolization has evolved as a sole treatment method or adjunct to surgical excision in the management of scalp AVMs with an excellent outcome. PURPOSE: To discuss minimally invasive techniques for treating scalp AVMs as well as to highlight the role of embolization before surgery. MATERIAL AND METHODS: This is a retrospective study of 50 patients with scalp AVM who underwent embolization (percutaneous/endovascular) during 2010-2019 at a tertiary care center. n-butyl cyanoacrylate (n-BCA) was used as an embolizing agent in all the cases and the patients were followed up at three- and six-month intervals with Doppler evaluation. RESULTS: A total of 50 patients were included in the study. The occipital region was the most common location; 82% were Schobinger class II lesions and 18% were class III lesions. Thirteen patients had small-sized AVMs and 37 patients had large-sized AVMs. Post-embolization surgery was performed in 36 patients. Of the patients, 28 underwent percutaneous embolization, 20 underwent endovascular embolization, and two underwent both to achieve complete embolization of the lesion. The number of percutaneous procedures increased in the latter half of the study period as the safety and efficacy of the technique were established. No major complications were seen in this study. CONCLUSION: Embolization of scalp AVMs is a safe and effective technique and can be used in isolation for small lesions and as an adjunct procedure to surgery for large-sized lesions.

Effect and Mechanism of Curdione Combined with Gemcitabine on Migration and Invasion of Bladder Cancer.

Bladder cancer (BCa), which usually occurs in bladder epithelial cells and is the fifth most common type of cancer in the world. he recurrence rate within 5 years after surgery is 0.8-45% of patients with early bladder cancer. Therefore, finding appropriate drug therapy for patients with bladder cancer can provide a reference for clinical treatment and play an important role in improving the prognosis of patients. In this study, CCK8 assay result showed that the inhibition of bladder cancer cell activity by Curdione and GEM increased with time and dose. Subsequently, CCK8, clone formation assay and Transwell result showed Curdione enhances GEM inhibition of bladder cancer cell activity, clonal formation and migration, these combine therapeutic schedule also could inhibited growth of in vivo xenograft tumors. The comprehensive database showed that CA2 is a potential target genes of Curdione, and Knockdown CA2 enhances GEM induced inhibition of cell proliferation and migration. Based on these advantages, Curdione may be a new type of action drug or adjunct for the treatment of bladder cancer.

The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment.

Bladder cancer (BCa) is associated with significant morbidity, with development linked to environmental, lifestyle, and genetic causes. Recurrence presents a significant issue and is managed in the clinical setting with intravesical chemotherapy or immunotherapy. In order to address challenges such as a limited supply of BCG and identifying cases likely to recur, it would be advantageous to use molecular biomarkers to determine likelihood of recurrence and treatment response. Here, we review microRNAs (miRNAs) that have shown promise as predictors of BCa recurrence. MiRNAs are also discussed in the context of predicting resistance or susceptibility to BCa treatment.

Looking for future biological control agents: the comparative function of the deutosternal groove in mesostigmatid mites.

The physics of fluid laminar flow through an idealised deutosternum assembly is used for the first time to review predatory feeding designs over 72 different-sized example species from 16 mesostigmatid families in order to inform the finding of new biological control agents. Gnathosomal data are digitised from published sources. Relevant gnathosomal macro- and micro-features are compared and contrasted in detail which may subtly impact the control of channel- or 'pipe'-based transport of prey liquids around various gnathosomal locations. Relative deutosternal groove width on the mesostigmatid subcapitulum is important but appears unrelated to the closing velocity ratio of the moveable digit. Big mites are adapted for handling large and watery prey. The repeated regular distance between deutosternal transverse ridges ('Querleisten') supports the idea of them enabling a regular fluctuating bulging or pulsing droplet-based fluid wave 'sticking' and 'slipping' along the groove. Phytoseiids are an outlier functional group with a low deutosternal pipe flow per body size designed for slot-like microchannel transport in low volume fluid threads arising from daintily nibbling nearby prey klinorhynchidly. Deutosternal groove denticles are orientated topographically in order to synergise flow and possible mixing of coxal gland-derived droplets and circumcapitular reservoir fluids across the venter of the gnathosomal base back via the hypostome to the prey being masticated by the chelicerae. As well as working with the tritosternum to mechanically clean the deutosternum, denticles may suppress fluid drag. Shallow grooves may support edge-crawling viscous flow. Lateral features may facilitate handling unusual amounts of fluid arising from opportunistic feeding on atypical prey. Various conjectures for confirmatory follow-up are highlighted. Suggestions as to how to triage non-uropodoid species as candidate plant pest control agents are included.

Circ_0002623 promotes bladder cancer progression by regulating the miR-1276/SMAD2 axis.

Circular RNAs (circRNAs) are key regulatory factors in the development of multiple cancers. This study is targeted at exploring the effect of circ_0002623 on bladder cancer (BCa) progression and its mechanism. Circ_0002623 was screened out by analyzing the expression profile of circRNAs in BCa tissues. Circ_0002623, miR-1276, and SMAD2 mRNA expression levels in clinical sample tissues and cell lines were detected through quantitative real-time polymerase chain reaction (qRT-PCR). After circ_0002623 had been overexpressed or silenced in BCa cells, the cell proliferation, migration, and cell cycle were evaluated by CCK-8, BrdU, Transwell assay, and flow cytometry. Tumor xenograft model was used to validate the biological function of circ_0002623 in vivo. Bioinformatics analysis and dual-luciferase reporter gene assay were conducted for analyzing and confirming, respectively, the targeted relationship between circ_0002623 and miR-1276, as well as between miR-1276 and SMAD2. The regulatory effects of circ_0002623 and miR-1276 on the expression levels of TGF-ß, WNT1, and SMAD2 in BCa cells were detected by Western blot. We reported that, in BCa tissues and cell lines, circ_0002623 was upregulated, whereas miR-1276 was downregulated. Circ_0002623 positively regulated BCa cell proliferation, migration, and cell cycle progression. Additionally, circ_0002623 could competitively bind with miR-1276 to increase the expression of SMAD2, the target gene of miR-1276. Furthermore, circ_0002623 could regulate the expression of TGF-ß and WNT1 via modulating miR-1276 and SMAD2. This study helps to better understand the molecular mechanism underlying BCa progression.

KDELR2-KIF20A axis facilitates bladder cancer growth and metastasis by enhancing Golgi-mediated secretion.

BACKGROUND: Bladder cancer (BCa) is a fatal form of cancer worldwide associated with a poor prognosis. Identifying novel drivers of growth and metastasis hold therapeutic potential for the disease. Transport homeostasis between the endoplasmic reticulum and Golgi and the secretion of matrix metalloproteinases (MMPs) mediated by Golgi have been reported to be closely associated with tumor progression. However, to date, mechanistic studies remain limited. RESULTS: Here, we identified KDELR2 as a potential risk factor with prognostic value in patients with BCa, especially those harbouring the KDELR2 amplification. In addition, we found that KDELR2 is a regulator of BCa cell proliferation and tumorigenicity based on bioinformatic analysis with functional studies. Mechanistically, we revealed that KDELR2 could regulate the expression of KIF20A, thus stimulating the expression of MMP2, MMP9 and MKI67. Functionally, the overexpression of KDELR2 and KIF20A markedly promoted proliferation, migration, and invasion in vitro and enhanced tumor growth in vivo, while knockdown of KDELR2 and KIF20A exerted the opposite effects. And the overexpression of KDELR2 also enhanced lymph node metastasis in vivo. CONCLUSIONS: Collectively, our findings clarified a hitherto unexplored mechanism of KDELR2-KIF20A axis in increasing Golgi-mediated secretion of MMPs to drive tumor progression in BCa.

Biocontrol strategies: an eco-smart tool for integrated pest and diseases management.

For the burgeoning global population, sustainable agriculture practices are crucial for accomplishing the zero-hunger goal. The agriculture sector is very concerned about the rise in insecticide resistance and the Modern Environmental Health Hazards (MEHHs) that are problems for public health due to on pesticide exposure and residues. Currently, farming practices are being developed based on microbial bio-stimulants, which have fewer negative effects and are more efficient than synthetic agro-chemicals. In this context, one of the most important approaches in sustainable agriculture is the use of biocontrol microbes that can suppress phytopathogens and insects. Simultaneously, it is critical to comprehend the role of these microbes in promoting growth and disease control, and their application as biofertilizers and biopesticides, the success of which in the field is currently inconsistent. Therefore, editorial is part of a special issue titled "Biocontrol Strategies: An Eco-smart Tool for Integrated Pest and Disease Management" which focuses on biocontrol approaches that can suppress the biotic stresses, alter plant defense mechanisms, and offer new eco-smart ways for controlling plant pathogens and insect pests under sustainable agriculture.

Mono-PEGylated thermostable Bacillus caldovelox arginase mutant (BCA-M-PEG20) induces apoptosis, autophagy, cell cycle arrest and growth inhibition in gastric cancer cells.

Gastric cancer is one of the most common malignant solid tumors in the world, especially in Asia with high mortality due to a lack of effective treatment. The potential usage of the newly constructed arginine-depleting enzyme-mono-PEGylated Bacillus caldovelox arginase mutant (BCA-M-PEG20), an effective drug against multiple cancer cell lines such as cervical and lung cancers, for the treatment of gastric cancer was demonstrated. Our results indicated that BCA-M-PEG20 significantly inhibited argininosuccinate synthetase (ASS)-positive gastric cancer cells, MKN-45 and BGC-823, while another arginine-depleting enzyme, arginine deiminase (ADI, currently under Phase III clinical trial), failed to suppress the growth of gastric cancer cells. In vitro studies demonstrated that BCA-M-PEG20 inhibited MKN-45 cells by inducing autophagy and cell cycle arrest at the S phase under 0.58 U/mL (IC50 values). Significant caspase-dependent apoptosis was induced in MKN-45 after the treatment with 2.32 U/mL of BCA-M-PEG20. In vivo studies showed that administrations of BCA-M-PEG20 at 250 U/mouse twice per week significantly suppressed about 50% of tumor growth in the MKN-45 gastric cancer xenograft model. Taken together, BCA-M-PEG20 demonstrated a superior potential to be an anti-gastric cancer drug.

UBE2T promotes proliferation, invasion and glycolysis of breast cancer cells by regualting the PI3K/AKT signaling pathway.

PURPOSE: Breast cancer (BCa) is one of the most common gynecological malignancies. Ubiquitin-coupled enzyme E2T (UBE2T) has been demonstrated to play crucial roles in various tumors. METHODS: UBE2T levels were detected using quantitative real time PCR and western blot. CCK-8 and colony formation assays were used to evaluate cell proliferation. A xenograft model was used to evaluate the effects of UBE2T on tumor growth in mice, and immunohistochemistry (IHC) assay was performed to detect the expression of UBE2T and Ki-67. Transwell assay was performed to determine cell migration and invasion. The ATP level, glucose consumption and lactate production were measured using the corresponding commercial kits. Western blot assay was used to detect the levels of epithelial-mesenchymal transformation (EMT), glycolytic and the PI3K/AKT pathway related proteins regulated by UBE2T. RESULTS: Upregulation of UBE2T expression in human BCa tissues was found in human clinical BCa tissues and The Cancer Genome Atlas (TCGA) dataset. The expression of UBE2T was confirmed to be up-regulated in BCa cells compared to normal breast epithelial cell line (MCF-10A). Overexpression of UBE2T promoted proliferation, migration, invasion and glycolysis in BCa cells, while UBE2T knockdown showed the opposite results. Moreover, UBE2T knockdown suppressed tumor growth in mice. Further mechanism analysis shows that UBE2T participated in the regulation of BCa progression through affecting the PI3K/AKT signaling pathway. CONCLUSION: UBE2T promoted proliferation, invasion and glycolysis through modulating PI3K/AKT signaling pathway in BCa, implying that UBE2T may provide a promising therapeutic target for the therapy of BCa.

Tomato Root Colonization by Exogenously Inoculated Arbuscular Mycorrhizal Fungi Induces Resistance against Root-Knot Nematodes in a Dose-Dependent Manner.

Arbuscular mycorrhizal fungi (AMF) are generally recognized to induce plant growth and prime plants against soil-borne parasites, such as plant parasitic nematodes. However, the effectiveness of commercial formulates containing AMF has been questioned. Increasing amounts per plant of one commercial AMF-containing formulate, reported in the text as Myco, were used to detect the effects on growth of tomato plants and the resistance induced against root-knot nematodes (RKNs) The doses used per plant (0.5, 1.0, 2.0 g, reported as Myco1, Myco2, Myco3, respectively) were soil-drenched to growing potted plants; the effects of such treatments were analyzed both in plants not inoculated or inoculated by Meloidogyne incognita juveniles. Consistent increases in plant weight were apparent as soon as 7 days only after Myco2 treatments. Moreover, only treatments with Myco2 induced a consistent repression of the nematode infection observed in untreated plants. Conversely, treatments with Myco1 and Myco3 did not produce such an early growth improvement; some plant weight increase was observable only at 28 dpt. Accordingly, such Myco doses did not restrict the level of infestation observed in untreated plants. Control of infection was dependent on the dose of Myco provided to plants five days before nematode inoculation. About one month after all Myco treatments, several areas of roots were found to be colonized by AMF, although in Myco2-treated plants, three genes involved in the AMF colonization process (SlCCaMK, SlLYK9, and SlLYK13) were found to be over-expressed already at 7 dpt; over-expression was generally less consistent at 14 and 21 dpt. The expressions of two key genes of plant defense, the hypersensitive cell death inducer PR4b gene and the glutathione peroxidase-encoding GPX gene, were monitored in roots of Myco2-treated plants 3 and 7 days after nematode inoculation. PR4b was over-expressed and GPX was silenced in treated plants with respect to untreated plants. The repressive effect of Myco2 treatment against RKN infection was completely abolished when Myco2 suspensions were autoclaved to sterilization or treated with the potent anti-fungal agent amphotericin B, thus indicating that the biological control agents contained in the commercial formulate were living fungi.