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Objective: Pigmented villonodular synovitis (PVNS) is a rare benign proliferative disease affecting the soft‐tissue lining the synovial joints and tendons. Its etiology is poorly understood, largely limiting the availability of current therapeutic options. Here, we mapped the synovial gene and protein profiles of patients with PVNS, revealed a link between synovial inflammation and invasion, and elucidated the potential molecular mechanism involved. Methods: The expression of synovial genes from 6 control individuals, 7 patients with osteoarthritis (OA), and 19 patients with PVNS was analyzed via RNA sequencing. Protein profiles from 5 control individuals, 10 patients with OA, and 32 patients with PVNS were analyzed using label‐free proteomics. Microarray and reverse transcription–polymerase chain reaction analyses and immunohistochemical staining were used to evaluate inflammatory cytokine and target gene expression levels in synovial tissue, epithelial cells, and synovial fibroblasts (FLSs) derived from tissue of patients with PVNS. Various signaling pathway inhibitors, small interfering RNAs, and Western blots were used for molecular mechanism studies. Transwell migration and invasion assays were subsequently performed. Results: In total, 522 differentially expressed proteins were identified in the tissues of patients with PVNS. By integrating RNA sequencing and microarray analyses, significant changes in the expression of epithelial–mesenchymal transition (EMT)‐related genes, including transforming growth factor TGF‐b induced, neural cadherin, epithelial cadherin, SNAIL, and TWIST, were confirmed in the tissue of patients with PVNS compared to the control tissue. In vitro, TGFβ induced EMT and increased epithelial cell migration and invasion. Moreover, TGFβ not only promoted interactions between epithelial cells and FLSs but also directly increased the migration and invasion abilities of FLSs by activating the classical Smad2/3 and nonclassical JNK/AKT signaling pathways. Conclusion: This study provides overall protein and gene profiles of PVNS and identifies the crucial role of TGFβ in synovial invasion pathology. Exploring the related molecular mechanism may also reveal a new strategy or target for PVNS therapy. [ABSTRACT FROM AUTHOR]

New technologies for more effective microbiological assays are being adopted by the food industry to intervene more rapidly in its production chain. The aim of this study was to evaluate the alternative methods of TEMPO® CAM and real-time PCR (rtPCR) Biotecon® in comparison with the ISO 10272-2:2017 reference method for Campylobacter spp. quantification in turkey meat, aiming to validate a quick and easily replicable method in these meat matrices. A total of 416 samples were analyzed over a one-year period. The TEMPO® methodology showed inadequate performance with a significant difference (p < 0.05) compared with the reference methodology; therefore, its use was not recommended for turkey meat matrices. However, the performance of the rtPCR Biotecon® methodology showed adequate performance with no significant difference (p > 0.05), and its use was recommended in turkey meat matrices. The study was limited to exclusive research in turkey meat matrices, and expansion of the research into other matrices is recommended to verify whether the behavior of alternative methodologies is similar. The findings of this study illustrate the necessity for a thorough and comprehensive evaluation during the implementation of alternative methodologies that may potentially supplant conventional approaches. [ABSTRACT FROM AUTHOR]

Objective: To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation. Methods: Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. Results: Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot. Conclusion: LK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Berberine, a phytochemical, possesses remarkable potential for multitargeted drug therapy in microbial infections, wound healing and anti-inflammatory applications. However, its clinical utility in skin and other diseases is constrained due to its high aqueous solubility and inadequate dermal and intestinal absorption, resulting in low absolute bioavailability. Objectives: The current investigation endeavors to develop a microemulsion loaded with berberine to enhance its solubility and therapeutic effects specifically for skin diseases, while comparing its efficacy with a simple emulsion. Materials and Methods: In this study, an optimized oil-in- water (o/w) type of emulsion and microemulsion were formulated utilizing berberine isolated from Berberis aristata roots, along with soy lecithin, oleic acid, Tween 80, and ethanol. The microemulsion and emulsion were subjected to characterization employing parameters such as FTIR, particle size, zeta potential, transmittance, viscosity, and stability. The formulations were assessed for their therapeutic effects through in vitro antioxidant, anti-inflammatory, and anti, microbial assays, encompassing six strains of micro, organisms comprising bacteria and fungi. Results: The investigation successfully generated a thermodynamically stable o/w type of microemulsion, which exhibited improved transparency and formed a clear solution. Characterization results, including particle size, zeta potential, viscosity, and conductivity measurements, fell within the acceptable range. The therapeutic evaluation demonstrated a substantial enhancement in the in vitro antioxidant, anti-inflammatory, and anti, microbial activity of berberine microemulsion compared to the plain berberine solution. Conclusion: This study concludes that berberine can be effectively incorporated into a microemulsion system. When topically applied, the microemulsion form exhibits significantly higher therapeutic efficacy against skin diseases compared to the conventional emulsion of berberine. [ABSTRACT FROM AUTHOR]

Aim: To identify an optimized strategy for the large‐scale production of nanovesicles (NVs) that preserve the biological properties of exosomes (EXOs) for use in periodontal regeneration. Materials and Methods: NVs from dental follicle stem cells (DFSCs) were prepared through extrusion, and EXOs from DFSCs were isolated. The yield of both extruded NVs (eNVs) and EXOs were quantified through protein concentration and particle number analyses. Their pro‐migration, pro‐proliferation and pro‐osteogenesis capacities were compared subsequently in vitro. Additionally, proteomics analysis was conducted. To further evaluate the periodontal regeneration potential of eNVs and EXOs, they were incorporated into collagen sponges and transplanted into periodontal defects in rats. In vivo imaging and H&E staining were utilized to verify their biodistribution and safety. Micro‐Computed Tomography analysis and histological staining were performed to examine the regeneration of periodontal tissues. Results: The yield of eNVs was nearly 40 times higher than that of EXOs. Interestingly, in vitro experiments indicated that the pro‐migration and pro‐proliferation abilities of eNVs were superior, and the pro‐osteogenesis potential was comparable to EXOs. More importantly, eNVs exhibited periodontal regenerative potential similar to that of EXOs. Conclusions: Extrusion has proven to be an efficient method for generating numerous eNVs with the potential to replace EXOs in periodontal regeneration. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of the GPER in cancer is controversial due to its dual anti and protumor effects. Elevated GPER expression in cervical cancer has been associated with improved survival outcomes. In cervical cancer cell lines, the selective GPER agonist G-1 induces cell cycle arrest and apoptosis, although the precise molecular mechanisms behind these effects are not fully understood. This study explores the impact of GPER activation by G-1 on the transcriptome, cell migration, and invasion in SiHa cells, as well as in non-tumorigenic keratinocytes transduced with HPV16 E6 or E7 oncogenes. G-1 has been shown to exert antitumor effects by activating apoptotic pathways and modulating migration and invasion processes. The findings support the GPER as a promising prognostic marker and suggest that G-1 could be a valuable therapeutic tool for treating cervical cancer. Background/Objectives: Estrogens and HPV are necessary for cervical cancer (CC) development. The levels of the G protein-coupled estrogen receptor (GPER) increase as CC progresses, and HPV oncoproteins promote GPER expression. The role of this receptor is controversial due to its anti- and pro-tumor effects. This study aimed to determine the effect of GPER activation, using its agonist G-1, on the transcriptome, cell migration, and invasion in SiHa cells and non-tumorigenic keratinocytes transduced with the HPV16 E6 or E7 oncogenes. Methods: Transcriptome analysis was performed to identify G-1-enriched pathways in SiHa cells. We evaluated cell migration, invasion, and the expression of associated proteins in SiHa, HaCaT-16E6, and HaCaT-16E7 cells using various assays. Results: Transcriptome analysis revealed pathways associated with proliferation/apoptosis (TNF-α signaling, UV radiation response, mitotic spindle formation, G2/M cell cycle, UPR, and IL-6/JAK/STAT), cellular metabolism (oxidative phosphorylation), and cell migration (angiogenesis, EMT, and TGF-α signaling) in SiHa cells. Key differentially expressed genes included PTGS2 (pro/antitumor), FOSL1, TNFRSF9, IL1B, DIO2, and PHLDA1 (antitumor), along with under-expressed genes with pro-tumor effects that may inhibit proliferation. Additionally, DKK1 overexpression suggested inhibition of cell migration. G-1 increased vimentin expression in SiHa cells and reduced it in HaCaT-16E6 and HaCaT-16E7 cells. However, G-1 did not affect α-SMA expression or cell migration in any of the cell lines but increased invasion in HaCaT-16E7 cells. Conclusions: GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia. [ABSTRACT FROM AUTHOR]

Objectives: Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier‐related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction. Materials and Methods: A CAL‐27‐LEC co‐culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability. Western blotting and RT‐qPCR detected protein and mRNA expression under different conditions, respectively. CCK‐8, scratch wound healing, and transwell assays revealed cell migration and proliferation. Tube formation experiment tested capacity for endothelial tube formation. Immunohistochemical staining analyzed tissue sections from 43 oral cancer individuals with/without diabetes. Results: In high‐glucose co‐culture system, we observed increased lymphatic barrier permeability and decreased expression of ZO‐1 and occludin, two tight‐junction proteins; conversely, the expression of PAR2, a high permeability‐related protein, was increased. Following linagliptin treatment, the expression levels of VEGF‐C, VEGFR‐3, and PAR2 decreased, while those of ZO‐1 and occludin increased. Considerably higher levels of LYVE‐1 expression in individuals with diabetes than in those without diabetes. Conclusions: By ameliorating the high glucose‐induced disruption of the lymphatic endothelial barrier, linagliptin may reduce lymphangiogenesis and exhibit an inhibitory effect on lymphatic metastasis in oral cancer patients with diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). Methods: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and gene set enrichment analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC. Results: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells; however, it did not influence the proliferation of cells. RNA sequencing and gene set enrichment analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival. Conclusions: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment. [ABSTRACT FROM AUTHOR]

Objectives We investigated the potential of serum proteins for distinguishing clinical and molecular subtypes in patients with GCA. Methods Proximity extension assays were used to analyse 1463 proteins in serum samples from patients with new-onset GCA (n  = 16) and patients who have achieved remission (n  = 13). Unsupervised and supervised cluster analyses were performed. Results Unsupervised cluster analysis identified three distinct clusters based on the protein signature. Compared with cluster 2, patients of cluster 1 had fewer PMR symptoms, increased levels of macrophage migration inhibitory factor (MIF) and pronounced NF-κB, STAT5 and IL-1 signalling. The changes in serum proteins upon remission differed between cluster 1 and 2. Patients with cranial GCA were characterized by altered endothelial and Th17 signalling, whereas patients not responding to treatment within the GUSTO-trial showed increased Th1 and diminished B cell signalling. Patients with anterior ischaemic optic neuropathy displayed higher levels of CHI3L1 (YKL40) and MMP12, and reduced levels of TIMP3. Conclusion Protein profiling identified patient clusters in GCA with distinct proteomic features and therefore likely different pathophysiology. These unique proteomic footprints might lead to more targeted treatments in future. [ABSTRACT FROM AUTHOR]

The study aims to evaluate the performance of Vitamin D/calcitriol-induced miR-589-3p in predicting the prognosis of cervical cancer patients and its role in cancer cell function. To identify differentially expressed miRNAs (DEMs) related to calcitriol treatment, the GSE61829 dataset was analyzed. MiR-589-3p expression levels were verified in cervical cancer patients. The association of miR-589-3p with overall survival was investigated using Kaplan-Meier survival analyses and the multi-variate Cox proportional hazards model analysis. The effects of miR-589-3p on cervical cancer cells and calcitriol-treated cells were examined using the MTT assay and Transwell migration/invasion assay. From GSE61829 dataset, a total of eleven DEMs were identified, including miR-589-3p. MiR-589-3p was found to be decreased in cervical cancer but increased after one-year intake of Vitamin D. Low miR-589-3p after one-year intake of Vitamin D was identified as a predictive factor for low survival probability (p = 0.0059) with a significant impact on the death risk (HR: 3.04; 95%CI: 1.47-6.29; p = 0.003). MiR-589-3p overexpression inhibited the proliferation and migration/invasion of cervical cancer cells and calcitriol-treated cervical cancer cells. In conclusion, miR-589-3p can be induced by Vitamin D/calcitriol treatment and inhibit cervical cancer progression. MiR-589-3p has the potential to predict overall survival in patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: Signal regulatory protein α (SIRPα) is found primarily on myeloid cells, including macrophages and neutrophils; binds to CD47; and regulates phagocytosis, antigen presentation, cellular fusion, cell proliferation, and migration. Therefore, SIRPα may be involved in the pathogenesis of autoimmune diseases, including systemic vasculitis. This study aimed to assess SIRPα expression in tissue samples from patients with vasculitis. Methods: Immunohistochemical staining for SIRPα was performed on temporal artery (TA), kidney, and lung biopsy samples from patients with giant cell arteritis (GCA), patients with microscopic polyangiitis (MPA), patients with granulomatosis with polyangiitis (GPA), and patients without vasculitis. A score of SIRPα+ expression was calculated, derived from the percentages of monocytes, macrophages, and dendritic cells and neutrophils with different staining intensities in affected tissues. Results: A total of 46 samples from patients with different vasculitides (GCA, MPA, and GPA) were included in the study. Tissue samples included TA samples from 15 patients with GCA; kidney samples from 11 and 9 patients with GPA and MPA, respectively; and lung samples from 11 patients with GPA. Most tissue samples from patients with active vasculitis (15 of 15 TA samples, 17 of 20 kidney samples, and 9 of 11 lung samples) showed SIRPα staining. SIRPα staining intensity was less in kidney samples compared to TA and lung samples. Conclusion: This study demonstrates high‐level expression of SIRPα in macrophages and monocytes in affected tissue in systemic vasculitis. These findings provide a foundation for further studies exploring the role of the SIRPα–CD47 pathway in the pathogenesis of systemic vasculitis and the potential for the blockade of SIRPα and/or the depletion of SIRPα+ cells as treatment of systemic vasculitis. [ABSTRACT FROM AUTHOR]

The research aimed to design, formulate and physiochemically evaluate toothpowder tablets using various herbs such as clove, cinnamon, ginger, amla and stevia by direct compression method as an eco-friendly alternative to traditional toothpaste. These small, bite-sized chewable tablets can be chewed into a paste before brushing, providing a similar effect to conventional oral toothpaste. Herbal toothpaste tablets were prepared in a dosage of 250 mg through direct compression. The powder blend was evaluation for various formulation characteristics, including bulk density, tapped density, angle of repose, compressibility index and Hausner's ratio. Post-compression characteristics, such as weight variation, hardness, pH, friability, foamability and disintegration were also assessed. The best formulations were selected based on acceptable pre-compression and post-compression properties and microbial assay results. Among all the formulations, the F3 formulations of 250 mg tablets were chosen as the best due to their favorable physicochemical characteristics. These formulated herbal toothpowder tablets offer a promising alternative to traditional toothpaste in improving oral hygiene. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate how L1 cell adhesion molecule (L1CAM) interacting with protein tyrosine kinase 2 (PTK2) affects endometrial cancer (EC) progression and determine its association with the focal adhesion kinase (FAK)–growth factor receptor-bound protein 2 (GRB2)–son of sevenless (SOS)–rat sarcoma (RAS) pathway. EC is a female cancer of major concern in the world, and its incidence has increased rapidly in recent years. L1CAM is considered a reliable marker of poor prognosis in patients with EC. Material and Methods: A single-center and prospective study was conducted using data from the Cancer Genome Atlas and samples from normal and EC tissues to explore the differential expression of L1CAM. Additional experimental models included human immortalized endometrial epithelium cells (hEECs) and EC cell lines such as KLE, RL95-2, and Ishikawa. L1CAM expression was regulated using lentiviruses designed for either overexpression or interference, and PTK2/focal adhesion kinase (FAK) signaling was inhibited with PF431396. Transfected KLE cells were injected into mice, and tumor growth was monitored over 14 days. Cellular proliferation and survival were assessed using cell counting kit, colony formation, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling assays. Metastatic behavior was evaluated through Transwell assays for cell migration and invasion. The expression levels of matrix metallopeptidase (MMP) 2 and MMP9 were determined by Western blot. In addition, the activation of the FAK–GRB2–SOS–RAS pathway was examined by assessing the protein levels of FAK, GRB2, SOS, and RAS. Results: There was a significant difference in L1CAM expression between EC tumor tissues and normal tissues, and L1CAM messenger RNA (1.85-fold) and L1CAM protein (2.59-fold) were significantly more expressed in EC tissues (P < 0.01) than in normal tissues. The tumor growth of L1CAM overexpressing EC cells was faster than that of negative control EC cells (6.43 fold; P < 0.001). L1CAM promoted the expression of FAK (1.43-2.72-fold; P < 0.001); enhanced EC cell proliferation (P < 0.01), survival and motility (P < 0.001), migration (P < 0.001), and invasion (P < 0.001); and activated the FAK–GRB2–SOS–RAS pathway, all of which were reversed when FAK expression was not upregulated (P < 0.001). Conclusion: By upregulating PTK2 and its encoded protein FAK, L1CAM was found to promote tumor progression and increase the activation of the FAK–GRB2–SOS–RAS pathway. These findings establish L1CAM and PTK2 as reference genes for poor prognostic prediction in EC and as targets for EC therapy, providing a valuable basis for distinguishing between benign and malignant endometrial conditions and justifying the necessity of targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Mosquito vector research and population control strategies are supported by the rearing of species like Aedes aegypti, commonly known for propagating yellow fever. Colonies of Ae. aegypti are typically reared on fresh animal bloods to supply nutrients including iron, sodium chloride, and albumin necessary for reproduction. However, fresh animal blood is difficult to handle, store, and transport, and its use in rearing is limited to two weeks post-collection. The present study reports on the identification of an inexpensive, shelf-stable spray-dried porcine blood (SDPB) product containing accessible hemoglobin that demonstrated usefulness in a simple mosquito alternative meal (AM) formulation. Quantitative evidence that the phagostimulant in SDPB is hemoglobin was obtained through chromatography assays and the elimination of other feeding stimulants as potential candidates. Ae. aegypti observably engorged upon and produced eggs when fed the AM, which was also shown to sustain multiple colony generations with offspring viable through the larval and pupal stages. SDPB-based AMs may develop into platforms for studying the rearing of hematophagous insects with the potential to expand the capabilities of resource-intensive population control strategies. Research into mosquito-borne illnesses faces hurdles because feeding fresh animal blood to rear female mosquitoes presents logistical, economic, and safety challenges. In this study, a shelf-stable additive (spray-dried porcine blood; SDPB) hypothesized to supply accessible hemoglobin was evaluated within an alternative meal (AM) containing whey powder and PBS for rearing the yellow fever mosquito Aedes aegypti. LC–MS/MS proteomics, microbial assays, and particle reduction techniques confirmed and characterized the functionality of hemoglobin in SDPB, while engorgement, fecundity, egg viability, and meal stability bioassays assessed AM performance. Chemical assays supported hemoglobin as the phagostimulant in SDPB with aggregates partially solubilized in the AM that can be more accessible via particle reduction. Unpaired two-tailed t-tests indicate that the AM stimulates oogenesis (t11 = 13.6, p = 0.003) and is stable under ambient (1+ y; t12 = 0.576, p = 0.575) and aqueous (14 d; t12 = 0.515, p = 0.639) conditions without decreasing fecundity. Egg hatch rates for the ninth generation of AM-reared Ae. aegypti were 50–70+%. With further development, this meal may serve as a platform for mass rearing or studying effects of nutritional additives on mosquito fitness due to its low cost and stability. Future work may examine tuning spray drying parameters and resulting impacts on hemoglobin agglomeration and feeding. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is one of the most common causes of death worldwide. Today, this disease does not have an effective treatment, leading to the exploration of novel pharmacological molecules. In this paper, we design and synthesize with a new synthetic route the lipophilic cation derived from gallic acid (TPP+C10) and gentisic acid (GA-TPP+C10), both able to reach mitochondria and uncouple the electron transport chain. Our results show that combining 5-fluorouracil with GA-TPP+C10 has a synergistic cytotoxic effect on CRC cells. Both compounds show antimigratory effects, decreasing signaling pathways and biomarkers. Our results show that mitochondrial agents could be an alternative to standard CRC drugs against this disease. Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC—such as 5-fluorouracil (5FU)—remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity. [ABSTRACT FROM AUTHOR]

Simple Summary: The naturally occurring derivative of estrogen, 2-methoxyestradiol (2-ME), has been shown to have good anti-cancer properties. However, it is broken down too quickly within the blood to be clinically useful. We designed 2-ME analogs with modifications which could avoid rapid metabolism, would preferably stay in the tumor, and were more toxic to cancer cells. Here, we looked more closely at how these compounds work within cancer cells, and how they communicate within themselves and with their environment. ESE-15-one and ESE-16 interfere with the functioning of the intracellular cytoskeleton (actin and microtubules), sending messages that stop cell division, intracellular transport of proteins, and cell migration and invasion, eventually inducing cell suicide. They also inhibited the movement of cells that make blood vessels that would support tumor growth. Using eggs with chicken embryos, we could show that the compounds reduced the tumor size and diminished the spread of cancer cells in a living system. The microtubule-disrupting agent 2-methoxyestradiol (2-ME) displays anti-tumor and anti-angiogenic properties, but its clinical development is halted due to poor pharmacokinetics. We therefore designed two 2-ME analogs in silico—an ESE-15-one and an ESE-16 one—with improved pharmacological properties. We investigated the effects of these compounds on the cytoskeleton in vitro, and their anti-angiogenic and anti-metastatic properties in ovo. Time-lapse fluorescent microscopy revealed that sub-lethal doses of the compounds disrupted microtubule dynamics. Phalloidin fluorescent staining of treated cervical (HeLa), metastatic breast (MDA-MB-231) cancer, and human umbilical vein endothelial cells (HUVECs) displayed thickened, stabilized actin stress fibers after 2 h, which rearranged into a peripheral radial pattern by 24 h. Cofilin phosphorylation and phosphorylated ezrin/radixin/moesin complexes appeared to regulate this actin response. These signaling pathways overlap with anti-angiogenic, extra-cellular communication and adhesion pathways. Sub-lethal concentrations of the compounds retarded both cellular migration and invasion. Anti-angiogenic and extra-cellular matrix signaling was evident with TIMP2 and P-VEGF receptor-2 upregulation. ESE-15-one and ESE-16 exhibited anti-tumor and anti-metastatic properties in vivo, using the chick chorioallantoic membrane assay. In conclusion, the sulfamoylated 2-ME analogs displayed promising anti-tumor, anti-metastatic, and anti-angiogenic properties. Future studies will assess the compounds for myeloproliferative effects, as seen in clinical applications of other drugs in this class. [ABSTRACT FROM AUTHOR]

Summary: A few Capsicum (pepper) species produce yellow‐colored floral nectar, but the chemical identity and biological function of the yellow pigment are unknown.A combination of analytical biochemistry techniques was used to identify the pigment that gives Capsicum baccatum and Capsicum pubescens nectars their yellow color. Microbial growth assays, visual modeling, and honey bee preference tests for artificial nectars containing riboflavin were used to assess potential biological roles for the nectar pigment.High concentrations of riboflavin (vitamin B2) give the nectars their intense yellow color. Nectars containing riboflavin generate reactive oxygen species when exposed to light and reduce microbial growth. Visual modeling also indicates that the yellow color is highly conspicuous to bees within the context of the flower. Lastly, field experiments demonstrate that honey bees prefer artificial nectars containing riboflavin.Some Capsicum nectars contain a yellow‐colored vitamin that appears to play roles in (1) limiting microbial growth, (2) the visual attraction of bees, and (3) as a reward to nectar‐feeding flower visitors (potential pollinators), which is especially interesting since riboflavin is an essential nutrient for brood rearing in insects. These results cumulatively suggest that the riboflavin found in some Capsicum nectars has several functions. [ABSTRACT FROM AUTHOR]

Recent research has established that the microbiome plays potential roles in the pathogenesis of numerous chronic diseases, including carcinomas. This discovery has led to significant interest in clinical microbiome testing among physicians, translational investigators, and the lay public. As novel, inexpensive methodologies to interrogate the microbiota become available, research labs and commercial vendors have offered microbial assays. However, these tests still have not infiltrated the clinical laboratory space. Here, we provide an overview of the challenges of implementing microbiome testing in clinical pathology. We discuss challenges associated with preanalytical and analytic sample handling and collection that can influence results, choosing the appropriate testing methodology for the clinical context, establishing reference ranges, interpreting the data generated by testing and its value in making patient care decisions, regulation, and cost considerations of testing. Additionally, we suggest potential solutions for these problems to expedite the establishment of microbiome testing in the clinical laboratory. [ABSTRACT FROM AUTHOR]

Tebuthiuron is a soluble and leachable herbicide that is highly used in crop fields in Brazil. Therefore, the aim of the present study was the analysis of the impact of tebuthiuron in the water. Through Winogradsky columns to replicate an aquatic environment contaminated with the xenobiotic compound, it was evaluated the toxicity of tebuthiuron in the microorganisms (bacteria, fungi, and algae). Phytotoxicity tests with Lactuca sativa seed were also done after eight weeks after the start of the assays with the columns. It was also carried out physicochemical characterization of the water from the columns throughout the experiments. The results proved that the herbicide did not affect the pH and the conductivity of the water. The microbiological assays showed that tebuthiuron affect directly the development and the number of cultivated bacteria, significantly reducing the number of CFU mL−1 and accelerating the death phase of the bacteria cells. Chlorophyll A results also confirmed the negative effect of the tebuthiuron in algae organisms, and the treatment with the highest concentration of tebuthiuron did not reach chlorophyll A values of the control even at the end of the eighth weeks of the tests. Even though diluted in water, tebuthiuron still showed to be harmful to L. sativa seeds, significantly inhibiting germination and root elongation when compared to the control. Therefore, it was possible to conclude that tebuthiuron affects the river and lake environments, eliminating algae, bacteria, and plant organisms present in this environment. [ABSTRACT FROM AUTHOR]

Ceftazidime is a beta-lactam that is used in the treatment of bacterial infections in humans and companion animals, such as dogs and cats. It is prescribed to treat gram-negative infections, especially those caused by Pseudomonas aeruginosa. This study aimed to compare the pharmacokinetics of ceftazidime using a microbiological assay to evaluate the adequacy of the proposed dosage regimens for susceptible gram-negative bacteria. For this purpose, five healthy mongrel male dogs, with a mean age of four years and an average weight of 19.1 kg, were administered a single intravenous bolus dose of ceftazidime (20 mg/kg). Plasma concentrations were measured using a microbiological assay, and dosage regimens were established by integrating pharmacokinetics data with pharmacodynamics parameters. The results showed that ceftazidime was rapidly distributed to the peripheral tissues (0.189 L/kg), with a half-life of 1.15 hours and a clearance rate of 0.166 L/hr./kg. The results obtained from the pharmacokinetics-pharmacodynamic integration suggested 20 mg/kg q8 hours of ceftazidime for susceptible gram- negative bacteria with a Minimum Inhibitory Concentration of ≤ 8 μg/ml, and 20 mg /kg q12 hours of ceftazidime for susceptible gram-negative bacteria with a Minimum Inhibitory Concentration of ≤ 4 μg/ml. In conclusion, a mild correlation was observed between the dogs’ weight and the ceftazidime half-life, which led to an adjustment of the proposed dosage regimen to 20 mg/kg q8 hours. [ABSTRACT FROM AUTHOR]

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• Nutritional aspects of the C. lanatus seeds were found as high for antioxidant activity. • Antimicrobial activity has higher affinity by the presence of various phytochemicals. • DPPH and FRAP antioxidant assays supported the radical scavenging activity. • The arrest of cell cycle of A549 cells in the G2 phase and cell viability were possessed to be greater in. • The ethanolic seed extract of C. lanatus has shown good anticancer potential against A549 cells. Cancer is a leading dangerous death-causing disease in millions over the world. It arises due to the uncontrolled growth of mal-functioned cells and formed as tumors. The disease can affect any part of the body. Still, it is a quest to find anti-cancer drugs which has been the major research endeavor around the globe. Traditionally humans use plants and their derived products as a source to cure various diseases. In recent years many researches had paved the way to use plant-based drugs. The current research aims to evaluate the anticancer activity of Citrullus lanatus seeds against A549 lung carcinoma epithelial cell lines. The study uses C. lanatus seeds which naturally contains antioxidants and phytochemicals that prevent cancer cell proliferation. The ethanolic seed extract of C. lanatus showed the presence of phytochemicals such as saponins, alkaloids, proteins and flavonoids by preliminary screening. The extract was tested for its anti-inflammatory showing 96.16 % at maximum concentration. The microbial assays also showed good signs of inhibition against the microorganisms by forming a zone of inhibition. The safety and efficacy of the extract were determined by MTT assay for the cytotoxicity using A549 cancer cell lines and non-cancerous cell lines. The IC50 concentration of C. lanatus seed extract showed dosage dependently at 51.73 μg/ml for A549 cell lines. They also resulted in significant induced cell cycle arrest and apoptosis at the G2 phase by inhibiting the A549 cell line proliferation. The present study works on lung carcinoma to find a better procurement in a traditional way that can develop future hope in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Background: Sulfotransferase family 2B member 1 (SULT2B1) has been reported to play oncogenic role in many types of cancers. Nevertheless, the role that SULT2B1 played in ovarian cancer (OC) and the hidden molecular mechanism is obscure. Methods: Expression of SULT2B1 in OC was analyzed by GEPIA database. qRT‐PCR and western blot (WB) was applied for the appraisement of SULT2B1 and Annexin A9 (ANXA9) in OC cell lines. The capabilities of cells to proliferate, migrate and invade were assessed with CCK‐8 assay, wound healing assay, along with transwell assay. Cell apoptotic level was estimated utilizing flow cytometry. WB was employed for the evaluation of migration‐ and apoptosis‐related proteins. Bioinformatic analysis and co‐immunoprecipitation were used to predict and verify the combination of SULT2B1 and ANXA9. Results: The data showed that SULT2B1 and ANXA9 were upregulated in OC cells. SULT2B1 depletion suppressed the proliferative, migrative, and invasive capabilities of SKOV3 cells but facilitated the cell apoptosis. SULT2B1‐regulated ANXA9 expression and were proved to bind to ANXA9. Additionally, ANXA9 deficiency exhibited the same impacts on cell migrative, invasive capability and apoptotic level as SULT2B1 silencing. Moreover, ANXA9 overexpression reversed the inhibitory impacts of SULT2B1 silencing on the proliferative, migrative, invasive, and apoptotic capabilities of SKOV3 cells. Conclusion: In summary, SULT2B1 silencing repressed OC progression by targeting ANXA9. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs), as emerging regulators of a wide variety of biological processes via diverse mechanisms, have been demonstrated to be of increasing importance in biology. Genome-wide association studies of tumor samples have identified several lncRNAs as either oncogenes or tumor suppressors in various types of cancers. In recent years, the importance of lncRNAs, especially in endometrioid cancer (EEC), has become increasingly well understood. The lncRNA Forkhead box P4 antisense RNA 1 (FOXP4-AS1) has been reported to fulfill roles in several types of cancers; however, the main biological function and associated underlying molecular mechanism of FOXP4-AS1 in EEC have yet to be fully elucidated. The present study therefore aimed to investigate how RNA FOXP4-AS1 may participate in the development and progression of endometrioid carcinoma tissues. Materials and Methods: In the present study, the expression level of FOXP4-AS1 was investigated in endometrioid carcinoma tissues and matching nearby normal endometrial tissues collected from patients receiving surgery at the hospital. A series of molecular biological assays were performed to investigate the effect of FOXP4-AS1 on cell proliferation, cell migration, and cell invasion. Results: An increased concentration of FOXP4-AS1 was identified in endometrioid carcinoma samples and cell lines compared with the corresponding controls, and this lncRNA was found to be positively correlated with advanced FIGO stages in patients with endometrial cancer. Furthermore, knocking down endogenous FOXP4-AS1 led to a significant reduction in the colony formation number and a significant inhibition of cell proliferation, cell migration, and cell invasion in endometrioid carcinoma cells. Moreover, dual-specificity phosphatase 5 (DUSP5), which is lowly expressed in endometrioid carcinoma tissues cells and negatively modulated by FOXP4-AS1, was identified as the downstream target molecule of FOXP4-AS1. Subsequently, the mechanistic experiments confirmed that, through binding to enhancer of zeste homolog 2 (EZH2; one of the catalytic subunits of polycomb repressive complex 2 [PRC2]), FOXP4-AS1 could epigenetically suppress the expression of DUSP5. Finally, the oncogenic function of the FOXP4-AS1/EZH2/DUSP5 axis in endometrioid carcinoma was confirmed via rescue assays. Conclusions: The findings of the present study have highlighted how FOXP4-AS1 fulfills an oncogenic role in endometrioid carcinoma, and targeting FOXP4-AS1 and its pathway may provide new biomarkers for patients with endometrioid carcinoma. [ABSTRACT FROM AUTHOR]

Xenotransplantation, transplantation into humans of vascularized organs or viable cells from nonhuman species, is a potential solution to shortages of transplantable human organs. Among challenges to application of clinical xenotransplantation are unknown risks of transmission of animal microbes to immunosuppressed recipients or the community. Experience in allotransplantation and in preclinical models suggests that viral infections are the greatest concern. Worldwide, the distribution of swine pathogens is heterogeneous and cannot be fully controlled by international agricultural regulations. It is possible to screen source animals for potential human pathogens before procuring organs in a manner not possible within the time available for surveillance testing in allotransplantation. Infection control measures require microbiological assays for surveillance of source animals and xenograft recipients and research into zoonotic potential of porcine organisms. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with appropriate protocols for microbiological monitoring of source animals and recipients. [ABSTRACT FROM AUTHOR]

Chemerin is a newly described adipokine with significant effects on obesity, metabolic disorders, and immune trafficking. Recently, chemerin has gained prominence for its potential roles in cancer and tumorigenesis with pro‐ or antitumor effects. To date, most referenced multifunctions of chemerin are attributed to the chemokine‐like receptor 1 (CMKLR1), distributing broadly in many tissues. This study investigates the in vitro roles of chemerin treatment on migration and invasion of ovarian carcinoma cells (OVCAR‐3 and SK‐OV‐3) and potential underlying mechanisms. Herein, exogenous chemerin treatment promotes growth and invasion of SK‐OV‐3 cells but has no significant effects on OVCAR‐3 cells. SK‐OV‐3 cells undergo morphological elongation characterized by epithelial‐to‐mesenchymal transition (EMT) and Ras homologous genome members A (RhoA)/Rho protein‐related curl spiral kinase‐1 (ROCK1) activation. Furthermore, chemerin‐enhanced invasion and EMT of SK‐OV‐3 cells are effectively blocked by C3 transferase (C3T) and Y27632 and RhoA and ROCK1 inhibitor, respectively. More importantly, RhoA/ROCK1‐EMT‐mediated SK‐OV‐3 cell invasion is orchestrated by CMKLR1 upregulation after chemerin treatment (50 ng/mL). The silencing of CMKLR1 significantly (P < 0.0001) reverses the chemerin‐enhanced invasion, EMT, and RhoA/ROCK1 activation of SK‐OV‐3 cells. Our study indicates that chemerin promotes invasion of OC cells via CMKLR1‐RhoA/ROCK1‐mediated EMT, offering a novel potential target for metastasis of OC. [ABSTRACT FROM AUTHOR]

Background: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. Purpose: To fabricate a tendon stem cell–derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. Study Design: Controlled laboratory study. Methods: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)–based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively. Results: TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL. Conclusion: TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation. Clinical Relevance: The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects. [ABSTRACT FROM AUTHOR]

Background: Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation. Methods: The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts. Results: The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis. Conclusion: The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties. [ABSTRACT FROM AUTHOR]

Baclofen is a food and drug administration approved medication to manage reversible spasticity, mainly targeting the relief of flexor spasms, clonus and concomitant pain, which are common issues following spinal cord lesions and multiple sclerosis. It can be administered orally or intrathecally. However, there is currently no standardised method for compounding the medication for oral administration, especially in paediatric patients or those with swallowing difficulties. It is often crushed and mixed with fruit juice or milk to aid in dosage adjustments and improve swallowability, potentially affecting the dosing accuracy. Therefore, this study aims to test the stability of extemporaneous suspension of baclofen at concentrations of 1 mg/ml and 10 mg/ml in X-Temp® oral suspension system. The suspension was stored in amber high density polyethylene bottles and stored either under refrigeration (5°±1°) or at room temperature (30°±1°) for duration of up to 90 d. The samples underwent thorough evaluation through visual inspection, pH measurement, high-performance liquid chromatography assay and microbiological stability assay. This study indicates that the baclofen suspension at concentrations of 1 mg/ml and 10 mg/ml remained consistent in physical, chemical, and microbiological characteristics for up to 90 d at both (5°±1°) and (30°±1°). Suggesting that the X-Temp® oral suspension system as a reliable medium for compounding of baclofen tablets. [ABSTRACT FROM AUTHOR]

Nowadays, a large number of aromatic and medicinal plants possess highly significant bioproperties, with numerous applications in medicine, pharmacy, cosmetology, and agriculture. This work aimed to conduct a phytochemical screening and assay of phytomarkers with biopharmaceutical potential and to assess the antioxidant and antibacterial activity of Persea americana Mill. kernel extracts in vitro. P. americana plant samples were collected in May 2017 in Kinshasa. Three standard strains were selected namely Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Pseudomonas aeroginosa ATCC 9027 for microbiological assays. The phytomarker assay was used to detect total polyphenols, and the antibacterial activity was determined using the solid diffusion method on the Mueller Hinton medium to establish the minimal inhibitory concentration. Antioxidant activity was evaluated by the DPPH, ABTS, and Phosphomolybdate techniques. The findings showed that P. americana kernels contain secondary metabolites such as flavonoids, polyphenols, alkaloids, tannins, and triterpenoids, which may confer interesting biological activities. Quantitative phytomarker analysis of P. americana extracts showed a concentration of 69.70±3.07 mg/QE of total polyphenols and 27.53±1.15 mg/QE of flavonoids. All the extracts tested had low antibacterial activity against the three strains tested. However, the methanolic extract showed better antioxidant activity. In view of the IC50 values of our various fractions, it is clear that P. americana kernels possess interesting antioxidant properties. [ABSTRACT FROM AUTHOR]

Background. The SUMO fusion system is advantageous in improving the solubility and correct folding of proteins that are difficult to produce. SUMO‐protease‐1 (Ulp1) is a key enzyme in this system, and its proper expression and purification in Escherichia coli BL21 (DE3) are critical to its efficiency. Objective. To optimize Ulp1 expression and purification using His6‐SUMO‐SDF‐1 as a model, aiming to improve efficiency across similar fusion proteins. Methods. We provided a codon‐optimized Ulp1 gene into the pET28a vector. Essential culture factors, including IPTG concentration, incubation length of time, and temperature, were precisely adjusted. Ulp1 was purified using Ni‐NTA affinity chromatography. A cleavage activity assay of recombinant Ulp1 is carried out using the His6‐SUMO‐SDF‐1 fusion protein to demonstrate how well the optimized settings work. Furthermore, the activity of recombinant SDF‐1 was evaluated using the scratch wound healing assay. Results. Ulp1 expression was optimized in E. coli using the pET28a vector, with optimum conditions including 0.1 mM IPTG, 28°C incubation temperature, and an overnight period of time. Recombinant Ulp1 was purified using Ni‐NTA affinity chromatography, resulting in high purity. Enzymatic activity was shown by the effective cleavage of the His6‐SUMO‐SDF‐1 fusion protein. In the scratch wound‐healing assay, recombinant SDF‐1 increased cell migration following cleavage, confirming that biological activity was retained. These findings illustrate Ulp1's efficient synthesis and effectiveness for prospective applications in biology. Conclusion. This study successfully showed the expression and purification of the recombinant Ulp1 enzyme, showing the most suitable growing conditions for productive protein production. Ulp1's functionality was validated by its specific cleavage of the His6‐SUMO‐SDF‐1 fusion protein, as well as the fragmented SDF‐1 purified and its biological activity in promoting cell migration. These findings highlight Ulp1's potential in protein processing as well as its application in biotechnological and biological research. [ABSTRACT FROM AUTHOR]

Nuclear migration through narrow constrictions is important for development, metastasis, and proinflammatory responses. Studies performed in tissue culture cells have implicated linker of nucleoskeleton and cytoskeleton (LINC) complexes, microtubule motors, the actin cytoskeleton, and nuclear envelope repair machinery as important mediators of nuclear movements through constricted spaces. However, little is understood about how these mechanisms operate to move nuclei in vivo. In Caenorhabditis elegans larvae, six pairs of hypodermal P cells migrate from lateral to ventral positions through a constricted space between the body wall muscles and the cuticle. P-cell nuclear migration is mediated in part by LINC complexes using a microtubule-based pathway and by an independent CDC-42 /actin-based pathway. However, when both LINC complex and actin-based pathways are knocked out, many nuclei still migrate, suggesting the existence of additional pathways. Here, we show that FLN-2 functions in a third pathway to mediate P-cell nuclear migration. The predicted N-terminal actin-binding domain in FLN-2 that is found in canonical filamins is dispensable for FLN-2 function; this and structural predictions suggest that FLN-2 does not function as a filamin. The immunoglobulin-like repeats 4–8 of FLN-2 were necessary for P-cell nuclear migration. Furthermore, in the absence of the LINC complex component unc-84 , fln-2 mutants had an increase in P-cell nuclear rupture. We conclude that FLN-2 functions to maintain the integrity of the nuclear envelope in parallel with the LINC complex and CDC-42 /actin-based pathways to move P-cell nuclei through constricted spaces. [ABSTRACT FROM AUTHOR]

Objectives: To assess the role of TNF‐α/TNFR2 axis on promoting angiogenesis in oral squamous cell carcinoma (OSCC) cells and uncover the underlying mechanisms. Materials and Methods: The expression of TNFR2 and CD31 in OSCC tissues was examined; gene expression relationship between TNF‐α/TNFR2 and angiogenic markers or signaling molecules was analyzed; the expression of angiogenic markers, signaling molecules, TNFR1, and TNFR2 in TNF‐α‐stimulated OSCC cells treated with or without TNFR2 neutralizing antibody (TNFR2 Nab) were assessed; the concentration of angiogenic markers in the supernatant of OSCC cells was detected; conditioned mediums of OSCC cells treated with TNF‐α or TNF‐α + TNFR2 Nab were applied to human umbilical vein endothelial cells (HUVECs), followed by tube formation and cell migration assays. Results: Significantly elevated expression of TNFR2 and CD31 in OSCC tissues was observed. A positive gene expression correlation was identified between TNF‐α/TNFR2 and angiogenic markers or signaling molecules. TNFR2 Nab inhibited the effects of TNF‐α on enhancing the expression of angiogenic factors and TNFR2, the phosphorylation of the Akt/mTOR signaling pathway, HUVECs migration, and tube formation. Conclusions: TNFR2 Nab counteracts the effect of TNF‐α on OSCC cells through the TNFR2/Akt/mTOR axis, indicating that blocking TNFR2 might be a promising strategy against cancer. [ABSTRACT FROM AUTHOR]

Background: BRD4, belonging to the bromodomain extra‐terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM. Methods: The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4‐depleted AM cells, RNA sequencing (RNA‐seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET‐inhibitors (BETi) was assessed with AM patient‐derived organoids. Results: Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient‐derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness‐associated pathways. Conclusion: BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness‐associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management. [ABSTRACT FROM AUTHOR]

This study aimed to develop yerba mate extracts (YME, Ilex paraguariensis) as active ingredients for a UVC‐light‐preserved (892 mJ/cm2; 50°C) sports drink (SD) and the sports gel derived from it (SG). Aqueous ultrasound‐assisted extractions (US; 20 KHz, 750 W) of yerba mate leaves were performed at varying temperatures (T: 20, 40, and 50 °C) and acoustic energy densities (AED: 0,.11, and.23 W/mL). Total polyphenol (TPC) extraction kinetics were characterized using the Spiro and Jago, Linares, and Peleg models. The Spiro and Jago model accurately described the extraction kinetic curves. An empirical correlation was found between its rate constant and the variables T and AED, reaching its maximum value at 50°C–.23 W/mL, with no further TPC extraction beyond 4 minutes (4.20 g GAE/L). For comparison purposes, the conditions 20°C/.23 W/mL/7 min (3.33 g GAE/L) and 100°C/0 W/mL/5 min (control) were also structurally and physiochemically compared. During the extraction, intraparticle diffusion was one of the major mechanisms limiting the extraction rate. With AED and T, the intraparticle coefficient increased significantly. The US‐assisted process generated extracts with greater wettability, hygroscopicity, more natural color, and similar content of relevant xanthin alkaloids and polyphenols, compared to the control. SEM micrographs revealed that the US‐assisted extract's porosity increased with AED and T. The UV‐C processing of SD was successfully validated through microbial challenge assays. YME (20°C/.23 W/mL/7 min) addition turned SD and SG greener and raised their flavonoid content (SD: 5.2‐fold and SG: 19.6‐fold) and TPC (SD: 5.5‐fold and SG: 5.3‐fold). The DPPH and ABTS total antioxidant activity for SD and SG increased by 3.1–3.4‐fold and 16.8–57.9‐fold, respectively. SD‐YM and SG‐YM were well‐accepted and described in a consumer field test. The developed YMEs can be a natural source of xanthine alkaloids and polyphenols, thereby replacing the synthetic additives typically employed in sports nutrition products. Practical applications: The growing consumer belief in natural extracts' ability to promote health and wellness is driving the global market for botanical extracts. Yerba mate (Ilex paraguariensis St Hill) is a healthier alternative to coffee and tea, with higher antioxidant capacity and proven health benefits. The proposed extraction method eliminates the need for high temperature and prolonged treatments, preserving the nutritional value of yerba mate leaves. Furthermore, it eliminates waste generation, perfectly aligning with sustainable practices. The optimized US‐assisted extraction resulted in high‐quality physicochemical extracts with significant functional activity. Amateur athletes are increasingly looking for products to enhance their performance that are both natural and effective. In this context, the developed extracts can serve as natural additives for sports nutrition products, which typically include synthetic caffeine and other compounds aimed at enhancing alertness, arousal, and energy. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE) is one of the most important neglected diseases and a public health concern worldwide. Due to the poor efficacy of current drugs, novel therapeutic approaches are urgently needed. Objectives: This study evaluated the scolicidal effects of the hydroalcoholic extract of Urtica dioica and the chloroformic extract of Pyrus boissieriana on protoscoleces of CE cysts. Methods: Protoscoleces were aseptically aspirated from the livers of sheep naturally infected with CE cysts. To assess the scolicidal effect of these herbal extracts, various concentrations of both extracts (5, 10, 20, 40, and 80 mg/mL) were added to a suspension of 3 x 10³ washed protoscoleces. After 10, 20, 30, 60, and 120 minutes of exposure, eosin stain was added to each tube, and the viability of protoscoleces was evaluated by flame cell motility under a light microscope, as well as impermeability to 0.1% eosin solution. All experiments were performed in triplicate. Results: The scolicidal effects of U. dioica extracts at a concentration of 80 mg/mL were 81% and 89% after 60 and 120 minutes of exposure, respectively. Almost the same results were obtained for P. boissieriana extracts at a concentration of 80 mg/mL (81.33% and 89% after 60 and 120 minutes of exposure, respectively), which were significantly different from the negative control group (P < 0.001). However, the extract of U. dioica exhibited stronger scolicidal effects compared to the extract of P. boissieriana at concentrations lower than 40 mg/mL (P < 0.001). Conclusions: The present findings indicate that both U. dioica and P. boissieriana extracts possess high protoscolicidal activities and could be used as alternative natural medicines in the treatment of CE. However, further studies are required to verify these findings through assessment in animal models and clinical subjects. [ABSTRACT FROM AUTHOR]

Specialized pro‐resolving lipid mediators (SPMs) are known for their anti‐inflammatory and pro‐resolving actions. The aim of the present study was to find new functions of the SPM resolvin D1n‐3 DPA (RvD1n‐3 DPA) on oral epithelial cells. As a starting point, we used a dataset obtained by RNA high‐throughput sequencing of oral epithelial cells exposed to TNF‐α and RvD1n‐3 DPA versus TNF‐α alone. GOrilla enrichment analysis showed that the actin cytoskeleton was significantly overrepresented after adjustment for multiple hypothesis testing. As actin, amongst others, is closely related to cell migration, we then explored whether RvD1n‐3 DPA can modulate oral epithelial cell migration. To this end, we used an in vitro cell migration model, including TNF‐α treatment, to mimic an inflammatory cell state. The analysis revealed that RvD1n‐3 DPA increased oral epithelial cell migration in the presence but not in the absence of TNF‐α. Addition of RvD1n‐3 DPA also induced F actin accumulation around the cell nucleus, indicating that RvD1n‐3 DPA potentially can mediate processes of intracellular transport. This indicates that this lipid mediator may be a promising therapeutic candidate in oral mucosal wound healing. [ABSTRACT FROM AUTHOR]

Background: Norway spruce (Picea abies) resin‐based products are used in human medicine. A resin‐based otic rinse also could be useful in supportive care of canine otitis externa (COE), yet information on its antimicrobial effect against canine pathogens or ototoxicity is lacking. Objectives: To investigate the antimicrobial properties and ototoxicity of a commercial resin‐based otic product. Materials and Methods: Antimicrobial effect was evaluated using a standardised challenge test on Staphylococcus pseudintermedius, Corynebacterium auriscanis, Pseudomonas aeruginosa, Escherichia coli, Malassezia pachydermatis, and Streptococcus halichoeri strains to measure reduction in growth after 24 h exposure to the product. Effect on cell morphology was investigated by exposing S. pseudintermedius, C. auriscanis, P. aeruginosa and M. pachydermatis to the product in 20% and 100% (v/v) concentrations for 6, 24 and 48 h, and evaluating cells by transmission (TEM) and scanning (SEM) electron microscopy. An in vitro microbial kill–rate assay also was performed. Auditory brain stem response test, clinical evaluation and postmortem histological evaluation of ear canals were undertaken on experimental guinea pigs treated with the test product or saline controls. Results: The product showed >log 5 growth reduction for all strains in the challenge test. TEM and SEM images showed clear changes in the cells' inner structures and deterioration of cells, and 100% (v/v) test product exposure induced microbial killing in 1–2 h. Ototoxicity was not detected in guinea pigs. Conclusions and Clinical Relevance: The product may be an option in supportive care of COE because of antimicrobial effects and lack of ototoxic properties in a guinea pig model. [ABSTRACT FROM AUTHOR]

Simple Summary: Cysteamine, an endogenously synthesized agent in mammalian cells and FDA-approved for cystinosis, shows promise as a safe anti-cancer agent by inhibiting tumor cell invasion and metastasis. Using computational analyses and multiple glioblastoma cell lines, we demonstrate the in vitro drug efficacy and molecular mechanism by which cysteamine inhibits tumor invasion and migration through targeting matrix metalloproteinase activity at micromolar concentrations. Our findings suggest that cysteamine could represent a novel therapeutic option for the treatment of glioblastoma patients. Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine's inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment. [ABSTRACT FROM AUTHOR]

The established potential of sodium alginate (SA) in tissue engineering and regenerative medicine underscores its significance. This study involved coating a sodium alginate substrate (SA) with nanofibers through the electrospinning of a polyvinyl alcohol (PVA) solution loaded with various antimicrobial agents, specifically silver nanoparticles (AgNPs). The coated nanofibers underwent comprehensive physiochemical, biological, and morphological characterization. The analysis of the coated nanofibers included techniques such as Field Emission Scanning Electron Microscopy (FESEM) and Fourier Transform Infrared Spectroscopy (FTIR). The contact angle was measured using the sessile drop method. Microbiological assays were conducted to evaluate the effectiveness against Staphylococcus aureus (S. aureus). Additionally, cell viability was assessed using MTT assays on the AD-MSC cell line. In vitro assays demonstrated the excellent biocompatibility of the coated nanofibers in cell culture. The SA/PVA/AgNPs-coated nanofibers exhibited inhibitory effects on the growth and proliferation of Staphylococcus aureus bacteria. The findings suggest that these novel coated nanofibers hold promise for the development of sustainable biomaterials for skin tissue engineering. [ABSTRACT FROM AUTHOR]

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Background and Objective: Enterococci are typically found in a healthy human gastrointestinal tract but can cause severe infections in immunocompromised patients. Such infections are treated with antibiotics. This study addresses the rising concern of antimicrobial resistance (AMR) in Enterococci, focusing on the prevalence of vancomycin-resistant enterococcus (VRE) strains. Materials and Methods: The pilot study involved 140 Enterococci isolates collected between 2021 and 2022 from two multidisciplinary hospitals (with and without local therapeutic drug monitoring protocol of vancomycin) in Latvia. Microbiological assays and whole genome sequencing were used. AMR gene prevalence with resistance profiles were determined and the genetic relationship and outbreak evaluation were made by applying core genome multi-locus sequence typing (cgMLST). Results: The acquired genes and mutations were responsible for resistance against 10 antimicrobial classes, including 25.0% of isolates expressing resistance to vancomycin, predominantly of the vanB type. Genetic diversity among E. faecalis and E. faecium isolates was observed and seven potential outbreak clusters were identified, three of them containing sequence types ST6, ST78 and ST80. The prevalence of vancomycin resistance was highest in the hospital without a therapeutic drug-monitoring protocol and in E. faecium. Notably, a case of linezolid resistance due to a mutation was documented. Conclusions: The study illustrates the concerning prevalence of multidrug-resistant Enterococci in Latvian hospitals, showcasing the rather widespread occurrence of vancomycin-resistant strains. This highlights the urgency of implementing efficient infection control mechanisms and the need for continuous VRE surveillance in Latvia to define the scope and pattern of the problem, influencing clinical decision making and planning further preventative measures. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.

Broad bean paste is a popular condiment in Asian countries. Leaves of Vitex negundo Linn. were used extensively in China during the koji-making of broad bean paste. Spreading V. negundo leaves on raw broad beans during fermentation was able to facilitate the rapid growth of fungi to form mature koji. We isolated two strains of fungi from mature koji, and four strains of bacteria from the rotten broad beans resulting from a failed attempt. According to microbial activity assays, two polymethoxylated flavones, 5-hydroxy-3,6,7,8,30,40-hexamethoxy flavone (HJ-1) and 5,40-dihydroxy-3,6,7,8,30- pentamethoxy flavone (HJ-2) were isolated from V. negundo leaves, and the fungal growth promotion and inhibition of bacterial growth of these two compounds were found to improve the production of broad bean koji. This study reveals the compounds present in V. negundo leaves with bioactivity against important microbes in koji manufacture, and provides a theoretical basis for the application of V. negundo in broad bean paste production. [ABSTRACT FROM AUTHOR]

Objective: Periostin (PN), a major matricellular periodontal ligament (PDL) protein, modulates the remodeling of the PDL and bone, especially under mechanical stress. This study investigated the requirement of PN‐integrin signaling in force‐induced expression of transforming growth factor‐beta 1 (TGF‐β1) and alpha‐smooth muscle actin (α‐SMA) in human PDL stem cells (hPDLSCs). Methods: Cells were stimulated with intermittent compressive force (ICF) using computerized controlled apparatus. Cell migration was examined using in vitro scratch assay. The mRNA expression was examined using real‐time polymerase chain reaction. The protein expression was determined using immunofluorescent staining and western blot analysis. Results: Stimulation with ICF for 24 h increased the expression of PN, TGF‐β1, and α‐SMA, along with increased SMAD2/3 phosphorylation. Knockdown of POSTN (PN gene) decreased the protein levels of TGF‐β1 and pSMAD2/3 upon force stimulation. POSTN knockdown of hPDLSCs resulted in delayed cell migration, as determined by a scratch assay. However, migration improved after seeding these knockdown cells on pre‐PN‐coated surfaces. Further, the knockdown of αVβ5 significantly attenuated the force‐induced TGF‐β1 expression. Conclusion: Our findings indicate the importance of PN‐αVβ5 interactions in ICF‐induced TGF‐β1 signaling and the expression of α‐SMA. Findings support the critical role of PN in maintaining the PDL's tissue integrity and homeostasis. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of mammalian‐enabled (Mena) on tongue squamous cell carcinoma (TSCC) metastasis and its mechanism. Materials and Methods: Immunochemistry was performed to investigate the Mena and tumor‐related markers expression, and its clinicopathological characteristics in 46 TSCC specimens. TSCC cell SCC9 and Cal27 untransfected or stable transfected with Mena overexpression and small interfering RNA were used to determine the role of Mena in cell proliferation, cell migration, invasion and metastasis, and EMT‐related markers in vitro, and the effect of Mena on TSCC growth and metastasis through tumor‐bearing and tumor metastasis immunodeficient mice models in vivo. Results: Immunochemistry showed that the expression of Mena was significantly correlated with lymphatic metastasis and TNM stage, E‐cadherin, Vimentin, and MMP2. Mena did not affect cell proliferation and colony formation in vitro, and tumor growth in vivo. However, it promoted cell migration and invasion in vitro, and TSCC metastasis in vivo. Conclusions: Mena expression is associated with lymphatic metastasis and tumor stage and promotes TSCC invasion and metastasis by inducing the EMT process. Thus, Mena may be a biomarker for prognosis and targeted therapy in TSCC patients. [ABSTRACT FROM AUTHOR]

Objective: Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral cavity. OSCC is aggressive and prone to metastasis; it is associated with high mortality and short survival. In this study, we investigated the function of the long non‐coding RNA LINC00525 in OSCC progression and the molecular mechanisms through in vitro and in vivo experiments. Materials and Methods: CCK8 assay was used to detect the effect of LINC00525 on cell viability; transwell migration and invasion assays and scratch assay were used to examine the role of LINC00525 in cell migration and invasion. Flow cytometry, RT‐PCR and western blot were used to detect apoptosis indexes. Tumorigenic effects were investigated using mouse xenograft tumour models. Results: LINC00525 was associated with OSCC survival and prognosis. LINC00525 knockdown decreased cell viability and epithelial‐mesenchymal transition (EMT) properties and increased apoptosis and also shortened the cell cycle of OSCC cells in vitro. The downregulation of LINC00525 reduced the growth of OSCC tumour in vivo. LINC00525 can regulate OSCC cells via the apoptotic signalling pathway. Conclusion: Our results indicate that LINC00525 exhibits oncogenic functions in OSCC. LINC00525 may be a new promising and potential target for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is a common male malignancy and the leading cause of cancer death in men. Long non-coding RNAs (lncRNAs), microRNA (miRNAs) and mRNAs networks mediate prostate cancer progression. Herein, we investigated the functions of lncRNA AC008972.1 and its regulatory mechanism in prostate cancer. Materials and Methods: The expression levels of lncRNA AC008972.1, miR-143-3p, and TAOK2 were detected in prostate cancer tissues and cell lines by reverse transcription–quantitative polymerase chain reaction. PC3 and LNCaP cells were used to establish lncRNA AC008972.1-knockdown, miR-143-3p-overexpressing, and thousand-and-one-amino acid 2 kinase (TAOK2)-downregulated cells. Cell viability was examined by MTT assays and cell proliferation was detected by clone formation assay. Cell migration and invasion were detected by wound scratch assay and transwell chamber assay. The apoptosis rate was analyzed by flow cytometry. The protein expression was detected by Western blot assay. The RNA interaction was explored and validated by RNA binding protein immunoprecipitation (RIP) assay and dual luciferase activity assay. A mouse xenograft model was established to investigate the effect of lncRNA AC008972.1 on prostate cancer progression. Results: High expression of lncRNA AC008972.1 was associated with low overall survival in prostate cancer patients. Downregulation of lncRNA AC008972.1 suppressed prostate cancer progression by inhibiting cell viability, proliferation, migration, and invasion, in addition to the EMT process, whereas cell apoptosis was significantly promoted. LncRNA AC008972.1 bound with miR-143-3p and negatively regulated miR-143-3p expression. MiR-143-3p overexpression suppressed prostate cancer malignant behaviors in vitro. TAOK2 expression was decreased by miR-143-3p through the complementary targeting of TAOK2 mRNA. Downregulation of lncRNA AC008972.1 mitigated prostate cancer malignant behaviors in vitro based on miR-143-3p/TAOK2 node. Furthermore, the data of xenograft model experiment showed that inhibition of lncRNA AC008972.1 suppressed tumor growth in vivo. Conclusions: Knockdown of lncRNA AC008972.1 inhibits prostate cancer cell growth via downregulation of TAOK2 induced by miR-143-3p. LncRNA AC008972.1 acts as an oncogene in the progression of prostate cancer and may provide a novel therapeutic target for prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of wild-type vesicular stomatitis virus strain (VSV-IN) on immunomodulation and tumour metastasis in mouse triple negative breast cancer (TNBC) 4T1 cell transplantation model mice. Methods: After VSV-IN infected 4T1 cells with MOI=1, MOI=10 and MOI=100 for 12, 24 and 48 h, 4T1 cell mortality was detected by CCK-8 method, migration ability by scratch healing assay, and the expressions of E-cadherin, MMP-2 and MMP-9 mRNA by qPCR. The fat pads of female BALB/c mice were inoculated with 0.1 mL of 4T1 cells with a cell density of 1x106 cells/mL to construct a 4T1 cell-loaded mouse model. When the tumour volume reached 200 mm³, the mice were injected intratumorally with PBS, taxol (TAX) (15 mg/kg), and VSV (1x106 pfu) once a week, respectively. After 4 administrations, mice were executed, stripped of intact grafted tumour tissues, and tumour volume and mass were measured. Histopathological sections of the lungs were stained with H-E, and tumour metastatic nodules of the lungs were observed. The proportion of T-cell subpopulations in the spleen was detected by flow cytometry. The levels of serum IL-6 and TNF-α were detected by ELISA. The expression levels of migration-related proteins in mammary gland tumours were analysed by using the online analysis of GEPIA. The expressions of MMP-2, MMP-9 and E-cadherin in mouse tumours were detected by immunohistochemistry, and the affinity of G and M proteins of VSV-IN and ERK2 and E-cadherin was predicted by protein-protein docking technology. Results: The mortality rate of 4T1 cells after 48 hours of VSV treatment at MOI=10 and 100 were significantly higher than that of the control group (P<0.01). Compared with that of the control group, the cell migration rate of the VSV-IN group (MOI=10) was significantly lower (P<0.01), and the relative expression of MMP-9 mRNA was significantly lower (P<0.05). Compared with those in the mice of the control group, transplanted tumours in the mice of the VSV-IN group grew more slowly, and their endpoint volume was significantly reduced (P<0.05). The number of lung metastatic nodules in the mice of the VSV group was significantly less than that of the control group ([12.86±1.86] vs [24±3.67], P<0.01). The proportions of splenic CD4+ T and CD8+ T cells in the VSV group were significantly higher (both P<0.05). The serum TNF-α and IL-6 levels were significantly higher (both P< 0.01). GEPIA tool analysis revealed that the expression levels of E-cadherin and MMP-9 were higher in breast cancer tissues than in paracancerous tissues (P<0.05). The expression of MMP-9 in the tumour cells of the mice in the VSV-IN group was significantly lower than that in the control group (P<0.05). The binding free energies of G and M proteins of VSV-IN to ERK2 were -11.7 kcal/mol and -6.4 kcal/mol, respectively. Conclusion: Wild-type VSV-IN inhibits the growth and metastasis of transplanted tumours in 4T1 tumor-bearing mice, which may be related to its promotion of anti-tumour immunity and modulation of the expression of migration-related proteins. [ABSTRACT FROM AUTHOR]