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The associability of artificial intelligence (AI) as a dual-use technology for nuclear material production (NMP) within the academic and practitioner communities remains widely neglected, and so a widening opportunity for AI to aid in illicit and covert non-peaceful applications exists. To address this emerging gap, this paper investigates the evolving and applicable uses of AI and finds broad evidence of its use to optimize performance, promote innovation, reduce costs, and enhance safety associated with the development and production of nuclear material. AI's use in this arena will, thereby, facilitate broader accessibility of peaceful uses of nuclear science and technology, while at the same time cause concerns that said improvements can aid the illicit development of nuclear weapons. As such, this paper advocates for a three-dimensional solution to manage the evolving dual-use concern of AI that involves advancing states-centric monitoring and regulation, promoting intellectual exchange between the nonproliferation sector and the AI industry, and encouraging AI industrial contributions. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) helps promote wound healing, but it is unclear whether it stimulates breast cancer cell proliferation, which restricts its application in breast cancer patients. This article explored the effect of PRP on breast cancer cell proliferation through preclinical experiments. Method: We cultivated MDA-MB-231 breast cancer cells with PRP in vitro. Subsequently, we employed Cell Counting Kit-8 (CCK-8) assays to assess their proliferation ability, wound healing assays to evaluate their migration ability, and Transwell assays to detect their invasion ability. Mouse breast cancer 4T1 cells were subcutaneously inoculated into nude mice. After tumor formation, PRP was injected around each tumor. Tumor size was measured. After 15 days, the tumors were surgically removed. Immunohistochemistry was used to detect key proteins involved in proliferation and apoptosis. Results: PRP inhibited the proliferation, migration, and invasion of MDA-MB-231 in vitro. After PRP was injected around tumors in nude mice, tumor growth slowed, Ki67 and phospho-histone H3 (pHH3) expression decreased, and Caspase 3 and Poly (adenosine diphosphate-ribose) polymerase 1 (PARP1) expression increased. Conclusion: The PRP inhibits the proliferation of breast cancer MDA-MB-231 and 4T1 cells. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a leading cause of cancer-related mortality, with a high rate of postoperative recurrence and poor long-term survival. The Eyes Absent (EYA) protein family plays a significant role in cancer progression, with EYA3 being implicated in promoting GC cell proliferation and tumor growth. Utilizing the DepMap database, we identified EYA3 as a gene of interest in GC. We analyzed EYA3 expression in GC tissues and cell lines, performed in vitro assays to assess its role in cell proliferation, and conducted gene set enrichment analysis to explore its relationship with autophagy and the mTORC1 signaling pathway. In vivo, we used a xenograft tumor model to examine the effects of EYA3 expression on tumor progression. EYA3 was consistently upregulated in GC tissues, and its high expression correlated with a decrease in patient survival rates. Silencing EYA3 in GC cell lines resulted in reduced cell proliferation. Inhibition of autophagy and activation of the mTORC1 signaling pathway were observed as mechanisms by which EYA3 may promote GC cell growth. In vivo experiments supported the in vitro findings, showing slower tumor growth with reduced EYA3 expression. Our study confirms the upregulation of EYA3 in GC and its association with poor prognosis. EYA3 promotes GC cell proliferation and tumor growth by activating the mTORC1 signaling pathway and inhibiting autophagy. These findings highlight the potential of EYA3 as a therapeutic target for GC, providing a foundation for future research and treatment strategies. Despite the promising data, the limitations of sample size and the need for further mechanistic studies are acknowledged. [ABSTRACT FROM AUTHOR]

Burn injuries, especially severe ones, causes microcirculation disorders in local wounds and distant tissues, leading to ischemia and hypoxia of body tissues and organs. The key to prevent and treat complications and improve prognosis after burns is to improve the state of ischemia and hypoxia of tissue and restore the blood supply of organs. Catalpol is an iridoid glycoside compound isolated from Rehmannia radix, which has been widely reported to have various of functions, including antioxidative stress, anti-inflammation, anti-apoptosis, and neuroprotection. However, the pharmacologic action and underlying mechanism of Catalpol in angiogenesis after burn injury remains unclear. The study investigated whether Catalpol regulates apoptosis and proliferation following vascular injury induced by burns using an in vitro model of oxygen-glucose deprivation (OGD) with a human umbilical vein endothelial (HUVE) cell line. The results showed that treatment with Catalpol reduces the level of apoptosis and promotes proliferation of endothelial cell. Mechanistically, Catalpol increases the expression of vascular endothelial growth factor (VEGF) by activating Hypoxia-inducible factor-1α (Hif-1α), resulting in increased expression of related downstream effector molecules. The current study suggested that Catalpol is a promising compound for endothelial protection in burns. It may be an efficient Hif-1α activator for endothelial cell deprived of oxygen and glucose. [ABSTRACT FROM AUTHOR]

Purpose: Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting the progression of various cancers. This article aims to elucidate the role of RNF6 in CC and its regulation of the Hippo-YAP1 signaling pathway. Methods: The public tumor dataset analyses, immunohistochemistry, and western blotting were used to explore the expression of RNF6 in CC. Gain- and loss-of-function assays were conducted to elucidate the role of RNF6 in the proliferation and invasion of CC cells. Transcriptome sequencing was used to explore RNF6's role in cervical cancer, with validation of its regulation of the Hippo-YAP1 pathway through western blotting and RT-qPCR. Co-transfection of YAP overexpression plasmids into RNF6-silenced CC cells were preformed to confirm YAP1's pivotal role in RNF6-mediated CC progression. Animal experiments were preformed to further validate RNF6 interference's inhibitory effect on CC proliferation in vivo. Results: Clinical samples and bioinformatics analysis revealed high expression of RNF6 in CC, and closely associated with advanced FIGO (International Federation of Gynecology and Obstetrics) stage, larger tumor size, and poor prognosis. Cellular functional experiments demonstrate that RNF6 promotes the proliferation, invasion, and migration of CC cells, while knockdown of RNF6 yields the opposite effect. Transcriptome sequencing further reveals that RNF6 may promote CC progression through the Hippo-YAP signaling pathway. Western blotting and RT-qPCR further unveil that RNF6 enhances the upregulation of YAP1 protein levels, thereby activating downstream oncogenes CTGF and CYR61 transcription. Additionally, exogenous overexpression of YAP1 reverses the inhibitory effect of RNF6 silencing on CC proliferation and invasion. Furthermore, RNF6 interference significantly attenuates tumor growth in vivo experiments. Conclusion: Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment. [ABSTRACT FROM AUTHOR]

Human babesiosis is a malaria‐like, tick‐borne infectious disease with a global distribution. Babesiosis is caused by intraerythrocytic, apicomplexan parasites of the genus Babesia. In the United States, human babesiosis is caused by Babesia microti and Babesia duncani. Current treatment for babesiosis includes either the combination of atovaquone and azithromycin or the combination of clindamycin and quinine. However, the side effects of these agents and the resistance posed by these parasites call for alternative approaches for treating human babesiosis. Proteases play several roles in the context of parasitic lifestyle and regulate basic biological processes including cell death, cell progression, and cell migration. Using the SYBR Green‐1 assay, we screened a protease inhibitor library that consisted of 160 compounds against B. duncani in vitro and identified 13 preliminary hits. Dose response assays of hit compounds against B. duncani and B. microti under in vitro conditions identified five effective inhibitors against parasite growth. Of these compounds, we chose ixazomib, a proteasome inhibitor as a potential drug for animal studies based on its lower IC50 and a higher therapeutic index in comparison with other compounds. Our results suggest that Babesia proteasome may be an important drug target and that developing this class of drugs may be important to combat human babesiosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Filamin B (FLNB) can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells. It can regulate the proliferation, differentiation and apoptosis of chondrocytes. However, the effect of FLNB on osteoblast proliferation, migration and apoptosis has not been reported. OBJECTIVE: To investigate the effect of FLNB on the proliferation, migration and apoptosis of MC3T3-E1 cells. METHODS: The adenoviral vectors for knockdown of FLNB expression (sh-FLNB1, sh-FLNB2, sh-FLNB3) were constructed and infected with MC3T3-E1 cells. After screened by puromycin drug, the efficiency of FLNB knockdown was detected by western blot and RT-PCR. The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments. The cells were divided into blank group, mc3t3 group, sh-NC group (empty vector), and sh-FLNB group (sh-FLNB lentivirus). The blank group was cultured in cell-free α-MEM complete medium; the mc3t3 group was cultured in α-MEM complete medium alone; and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin. After 3 days of culture, cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1; flow cytometry was used to detect cell apoptosis; and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION: Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3 (P < 0.000 1), which was used as a stable cell line for subsequent experiments. Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB (P < 0.05). Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB. Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB, the expression of pro-apoptotic factor Bax increased significantly, and the expression of anti-apoptotic factor Bcl-2 decreased significantly (P < 0.05). To conclude, knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells, decrease the migration ability of the cells, and increase cell apoptosis. [ABSTRACT FROM AUTHOR]

The Patient-Derived Organoids (PDOs) has demonstrated significant potential in personalized medicine. However, the initial establishment of lung cancer organoids (LCOs), and timely therapeutic recommendations face several challenges. Particularly, the current culture systems have not yet achieved the capability to long-term cultivation of all lung tumor sample sources, including malignant pleural effusion (MPE), which poses significant barriers to the rapid clinical translation of PDOs. Here, we established a LCOs biobank derived from various tumor cell origins and investigated the impact of supplementing culture media with MPE supernatant on organoid formation, culture duration, and drug sensitivity. Our findings indicate that MPE can enhance the successful rate of LCOs by extending the passage number and promoting the initial formation of difficult-to-culture samples, such as those derived from MPE or cell lines that were previously unsuccessful in Airway Organoid (AO) medium. MPE also facilitates the rapid proliferation of LCOs, reducing the culture duration by over 50%. Additionally, LCOs exhibit increased chemoresistance in the presence of MPE, which modifies stem cell distribution and reshapes the internal structure of the organoids. Overall, this study highlights the significance of MPE in facilitating the establishment and maintenance of LCOs, and its potential for translational applications in lung cancer research and personalized. [ABSTRACT FROM AUTHOR]

Low fluid shear stress (FSS, ≤ 2 dyn/cm2) has been shown to exert protective effects on chondrocytes, but the underlying molecular mechanisms remain unclear. This study aimed to elucidate the mechanisms by which FSS promotes chondrocyte proliferation and extracellular matrix (ECM) stability. We exposed SW1353 chondrocytes to low FSS (1.8 dyn/cm2, 60 min) and found that it led to a significant downregulation of microRNA-143-3p (miR-143-3p), which was associated with increased chondrocyte proliferation and ECM secretion, including type II collagen (COL2A1) and aggrecan. Further investigation revealed that miR-143-3p directly targeted ERK5, a key component of the ERK5/KLF4 signaling pathway. Overexpression of miR-143-3p suppressed ERK5/KLF4 pathway activation, resulting in reduced chondrocyte proliferation and ECM production. Our findings demonstrate that low FSS promotes chondrocyte proliferation and ECM secretion by downregulating miR-143-3p, leading to the activation of the ERK5/KLF4 signaling pathway. This study reveals a novel mechanism by which FSS regulates chondrocyte behavior and ECM secretion, highlighting the potential of FSS as a therapeutic target for cartilage-related diseases. [ABSTRACT FROM AUTHOR]

Recent studies have uncovered that TIPE2 is involved in the development of cancer. However, less research has been conducted on the role of TIPE2 in melanoma. Our study aims to elucidate the mechanism of action of TIPE2 in the development of melanoma. We examined TIPE2 expression in paracarcinoma tissue and melanoma tissues and found that TIPE2 expression was downregulated in melanoma tissue compared with paracarcinoma tissue. Overexpression of TIPE2 significantly inhibited the proliferation of melanoma cells in vitro and even inhibited tumor formation in vivo. The CCK8 assay results indicated that TIPE2 overexpression suppressed the proliferation of melanoma cells. The colony-forming ability and wound healing ability of TIPE2-overexpressing melanoma cells were significantly reduced compared with those of control cells. Moreover, immunohistochemistry experiments using a nude mouse tumor model showed consistent results. TIPE2 inhibited the phosphorylation of MEK and ERK. In summary, TIPE2 suppresses the proliferation and migration of melanoma cells by affecting proliferation-related factors and possibly by regulating the MEK/ERK pathway. TIPE2 could be used to inhibit melanoma growth and is a potential drug target for future drug development. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of varieties of tumors. Previous studies have shown that lncRNA GClnc1 is highly expressed in osteosarcoma (OS). However, the mechanism of lncRNA GClnc1 in osteosarcoma has not been fully elucidated. In this study, we investigated the biological roles of lncRNA GClnc1 in osteosarcoma and unveiled its underlying mechanisms. Methods: The expression of lncRNA GClnc1 in OS cells was detected by real-time quantitative PCR (qRT-PCR). The functional roles of lncRNA GClnc1 were examined by CCK8, trans-well, scratch wound healing assay, colony formation, and apoptosis assays in osteosarcoma cells upon silencing or overexpressing GClnc1. Western blot analysis, qRT-PCR, and RNA co-immunoprecipitation (RIP) assays were used to detect the interaction between lncRNA GClnc1 and NONO. Results: The expression of lncRNA GClnc1 was up-regulated in osteosarcoma cell lines. Knockdown of lncRNA GClnc1 suppressed the cell growth, migration, and invasion of OS cells, whereas the over-expression of GClnc1 improved the proliferation, migration, and invasion of OS cells. Mechanistically, we identified that lncRNA GClnc1 regulates the stability of NONO by blocking FBXW7-mediated ubiquitination degradation. Additionally, overexpression of NONO can reverse GClnc1 silencing exerted suppression of the cell proliferation, migration, and invasion, and vice versa. Conclusions: Our study elucidated that lncRNA GClnc1 participates in the progression of OS by regulating the NONO signal pathway. Targeting GClnc1 provides a potential target for future clinical treatment of OS. [ABSTRACT FROM AUTHOR]

Purpose: Cancer treatments often become ineffective because of acquired drug resistance. To characterize changes in breast cancer cells accompanying development of resistance to inhibitors of the oncogenic transcription factor, FOXM1, we investigated the suppression of cell death pathways, especially ferroptosis, in FOXM1 inhibitor-resistant cells. We also explored whether ferroptosis activators can synergize with FOXM1 inhibitors and can overcome FOXM1 inhibitor resistance. Methods: In estrogen receptor-positive and triple-negative breast cancer cells treated with FOXM1 inhibitor NB73 and ferroptosis activators dihydroartemisinin and JKE1674, alone and in combination, we measured suppression of cell viability, motility, and colony formation, and monitored changes in gene and protein pathway expressions and mitochondrial integrity. Results: Growth suppression of breast cancer cells by FOXM1 inhibitors is accompanied by increased cell death and alterations in mitochondrial morphology and metabolic activity. Low doses of FOXM1 inhibitor strongly synergize with ferroptosis inducers to reduce cell viability, migration, colony formation, and expression of proliferation-related genes, and increase intracellular Fe+2 and lipid peroxidation, markers of ferroptosis. Acquired resistance to FOXM1 inhibition is associated with increased expression of cancer stem-cell markers and proteins that repress ferroptosis, enabling cell survival and drug resistance. Notably, resistant cells are still sensitive to growth suppression by low doses of ferroptosis activators, effectively overcoming the acquired resistance. Conclusion: Delineating changes in viability and cell death pathways that can overcome drug resistance should be helpful in determining approaches that might best prevent or reverse resistance to therapeutic targeting of FOXM1 and ultimately improve patient clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA), a chronic autoimmune condition, is characterized by persistent synovial inflammation, bone degradation, and progressive joint deterioration. Despite considerable research efforts, the precise molecular mechanism underlying RA remains elusive. This investigation aims to elucidate the potential role and molecular mechanism of N6-methyladenosine (m6A) methylation regulators in the pathogenesis of RA. Methods: In this study, we employed bioinformatics tools to elucidate the association between RA and m6A modifications, aiming to identify potential biological markers. We extracted datasets GSE12021, GSE55235, and GSE55457 from the Gene Expression Omnibus (GEO) database for comprehensive analysis. Utilizing differential expression analysis, protein-protein interaction (PPI) analysis, and single-cell sequencing techniques, we identified pivotal hub genes implicated in the pathogenesis of RA. Subsequently, we assessed the correlation between these hub genes and the pathogenesis of RA using Gene Set Enrichment Analysis (GSEA). Both in vivo and in vitro experiments were performed to confirm the expression and functional roles of the identified key hub gene in RA. Results: Differential expression analysis, PPI analysis, and single-cell analysis identified three key hub genes (YTHDC1, YTHDC2, and YTHDF2) associated with RA. GSEA results further revealed that these genes are enriched in pathways associated with inflammatory responses. Subsequent correlation analysis demonstrated a significant negative correlation between YTHDC1 expression and CD8+ T cell levels. Notably, the gene and protein expression levels of YTHDC1 and YTHDF2 were significantly reduced in the synovial tissue of RA patients. Furthermore, silencing YTHDC1 in fibroblast-like synoviocytes (FLSs) significantly inhibited their migration, invasion, proliferation, and induced apoptosis. Conclusion: YTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells, but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE: To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments, and to explore the regulatory role of CCR1 and CXCR4. METHODS: Human bone marrow mesenchymal stem cells were selected as experimental subjects. CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells. Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment, respectively. The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology. Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION: (1) 5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells, and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency. (2) To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells, 5 and 10 μmol/L quercetin were selected for the subsequent experiments, and ligustrazine was used as the positive control drug, and the experiments were divided into blank control group, 5 μmol/L quercetin group, 10 μmol/L quercetin group, and 100 μmol/L ligustrazine group. (3) In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment, and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group. (4) The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4. (5) Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA. (6) This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most common lung cancer subtype, and the prognosis of affected patients is generally poor. The traditional Chinese medicine Uncaria rhychophaylla has been reported to exhibit anti-lung cancer properties. Accordingly, the main bioactive ingredient in Uncaria rhychophaylla, Corynoxine, may hold great value as a treatment for lung cancer. Methods: The impact of Corynoxine on the viability of LUAD cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in A549 cells was evaluated via flow cytometry. Migration and invasion capabilities were determined through wound healing and Transwell assays, respectively. The key pathways targeted by Corynoxine in LUAD were identified using a network pharmacology approach. Additionally, Western immunoblotting, quantitative real-time PCR (qRT-PCR), and ELISA assays were conducted to validate the underlying mechanisms. The in vivo anti-tumor efficacy of Corynoxine was assessed in xenograft nude mice. Results: In this study, Corynoxine treatment was found to markedly suppress in vitro LUAD cell proliferative, migratory, and invasive activity. It additionally downregulated Vimentin and promoted E-cadherin upregulation consistent with the disruption of epithelial-mesenchymal transition (EMT) induction while also accelerating apoptotic death. Furthermore, network pharmacology analysis revealed that the PI3K/AKT pathway is a potential target of Corynoxine in LUAD. In vitro assays demonstrated that treatment with Corynoxine resulted in the suppression of PI3K/AKT signaling and a consequent drop in cyclooxygenase-2 (COX-2) expression. These findings were further confirmed in vivo in mice harboring A549 tumor xenografts in which Corynoxine was able to interfere with the PI3K/AKT/COX-2 signaling axis. Conclusion: This study elucidated the potential effects of Corynoxine in suppressing proliferation and metastasis in LUAD, along with investigating the underlying mechanisms. These data highlight the promise of Corynoxine as a novel therapeutic tool for the treatment of individuals diagnosed with LUAD. [ABSTRACT FROM AUTHOR]

Antigen-driven T-cell proliferation is often measured using fluorescent dye dilution assays, such as the CFSE-based proliferation assay. Dye dilution assays have been powerful tools to detect human CD4+ T-cell responses, particularly against autoantigens. However, it is not known how many cells within the proliferating population are specific for the stimulating antigen. Here we determined the frequency of CD4+ T cells specific for the stimulating antigen within the antigen-responsive population of CFSE-based proliferation assays. We compared CD4+ T-cell responses to a type 1 diabetes autoantigen (proinsulin C-peptide) and to a vaccine antigen (tetanus toxoid). The TCRs expressed by antigen-responsive CD4+ T cells were sequenced, and their antigen specificity was tested functionally by expressing them in a reporter T-cell line. Responses to C-peptide were weak, but detectable, in PBMC from individuals with T1D, whereas responses to tetanus toxoid were much stronger. The frequency of antigen-specific CD4+ T cells correlated with the strength of the response to antigen in the proliferation assay. However, antigen-specific CD4+ T cells were rare among antigen-responsive CD4+ T cells. For C-peptide, an average frequency of 7.5% (1%–11%, n = 4) of antigen-responsive CD4+ T cells were confirmed to be antigen specific. In the tetanus-toxoid-stimulated cultures, on average, 45% (16%–78%, n = 5) of the antigen-responsive CD4+ T cells were tetanus toxoid specific. These data show that antigen-specific CD4+ T cells are a minority of the cells that proliferate in response to antigen and have important implications for in vitro CD4+ T-cell proliferation assays. [ABSTRACT FROM AUTHOR]

Objective: Long non-coding RNAs (lncRNAs) LINC02466 is an lncRNA newly linked to the adverse outcomes in primary liver cancer patients, and its crucial involvement in the disease's escalation. Decoding the specific role of LINC02466 in HCC progression is of great significance to provide a potential therapeutic target for HCC. Methods: RT-qPCR and Western Blot techniques was used to analyze the expression levels of LINC02466 in both malignant and surrounding healthy liver tissues. CCK8 assays and colony formation experiments indicates the LINC02466's effect on the proliferation rates of liver cancer cells. Flow cytometry was pivotal in revealing its significant influence on the cell cycle of these cells. Kaplan–Meier survival analysis with log-rank tests were employed. Results: The suppression of LINC02466 markedly reduces the stemness attributes of liver cancer cells, indicating a potential therapeutic target. LINC02466 overexpression significantly increased tumor growth rates and final volumes. Further research indicated that LINC02466 significantly influences liver cancer progression through regulating the mTOR signaling pathway. Conclusion: LINC02466 regulating cell proliferation, the cell cycle, and stemness characteristics via the mTOR pathway, suggesting LINC02466 as a potential therapeutic target for primary liver cancer. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidences have stressed the association between hypoxanthine phosphoribosyl transferase 1 (HPRT1) overexpression and the poor prognosis of various cancers. Our study, herein, preliminarily investigates the involvement of HPRT1 in nasopharyngeal carcinoma (NPC). Methods: Data from TCGA were applied to read HPRT1 expression in diverse cancers including NPC and to predict the prognosis of NPC patients. The total RNA and protein from NPC cells and nasopharyngeal epithelial cells NP460 were extracted to quantify HPRT1 expression. Following the completion of transfection, the proliferation and migration of NPC cells were determined employing MTT, colony formation and western blot assay (the quantification on expressions of protein related to proliferation and migration). Results: HPRT1 was differentially expressed in diverse cancers yet particularly highly expressed in NPC, and high HPRT1 expression was related to the poor prognosis of NPC patients. Also, HPRT1 expression was higher in NPC cells and its silencing diminished the viability and proliferation of NPC cells and reduced the expressions of CyclinD1, CyclinE, Multidrug Resistance Protein 1 (MDR1), matrix metalloproteinase (MMP)-2, and MMP-9. Conclusion: This study preliminarily explored the involvement of HPRT1 in NPC based on some cellular assays in vitro, which may provide evidence for investigating the specific mechanism underlying the effects of HPRT1 in cancers. [ABSTRACT FROM AUTHOR]

In the brains of adult rodents, the cells arising in the subventricular zone of the lateral ventricles maintain the ability to divide when migrating to the olfactory bulb along the rostral migratory stream (RMS). Dividing cells in the RMS are most frequently revealed through immunohistochemical detection of an exogenous marker of proliferation, 5-Bromo-2-deoxyuridine (BrdU), which incorporates into DNA during the S-phase of mitosis. The more recently recognized antigen Ki-67 (also known as Kiel-67 and MKI67), an endogenous protein expressed in nuclei at all stages of mitosis, is also used for proliferation detection. BrdU and Ki-67 are often used as alternative methods, but they have not previously been compared in the RMS. We analyzed the numbers and distribution of cells labeled either with BrdU or Ki-67 within the RMS of adult rats. The first group of animals received a single i.p. dose of BrdU. In the second group, dividing cells were visualized by Ki-67 immunohistochemistry. Some sections from brains of BrdU-treated rats were also immunostained for Ki-67. Labeled cells were counted in the three anatomical parts of the RMS (vertical arm, elbow and horizontal arm) using a method for unbiased estimation of cell density. The distribution of proliferating cells was similar for both markers. Most BrdU and Ki-67 positive cells were located in the vertical arm and in the elbow, but a caudo-rostral reduction in cell divisions was more evident with Ki-67 labeling. The number of Ki-67 positive cells significantly exceeded the number of BrdU positive cells in all parts of the RMS. Our results indicate that BrdU and Ki-67 are not interchangeable markers for evaluation of proliferative activity in the RMS. [ABSTRACT FROM AUTHOR]

Brucella abortus (B.abortus) is a zoonotic bacterial pathogen that causes chronic host infections. The eradication of brucellosis using antibiotic therapy is often incomplete or slow. In a mouse model, the predominance of alternatively activated macrophages (also known as M2) plays an essential role in sustaining chronic infection. The underlying functional mechanism by which M2 sustains chronic infection remains unclear. Here, we show that B. abortus can enter M2 via triggering receptor expressed on myeloid cells 2 (TREM2) and promotes the upregulation of TREM2 expression of M2 in a type IV secretion system (T4SS)- dependent manner. Increased TREM2 enhances B. abortus growth within M2 by suppressing intracellular ROS production, preventing M2 pyroptosis via suppression of mitochondrial ROS (mROS), and promoting M2 proliferation by increasing b-catenin expression. In line with these results, downregulation of TREM2 expression suppressed B. abortus intracellular growth and M2 proliferation and induced M2 pyroptosis. In our mouse model, upregulation of TREM2 expression sustained the accumulation of M2 and B. abortus chronic infection, whereas downregulation of TREM2 expression restricted M2 proliferation and chronic infection. Collectively, our results suggest that targeting TREM2 may be a potential adjunct to antibiotic therapy for the prevention of chronic Brucella infection. [ABSTRACT FROM AUTHOR]

Six new derivatives were synthesized by reacting the alkaloid songorine (1) with isocyanates. Their structures were confirmed by IR, mass, 1H and 13C NMR spectral methods. The effects of the obtained compounds on tumor cell growth in vitro were studied. 21-Ethyl-1-O-3′-chlorophenylcarbamate-15-hydroxy-4-methyl-16-methylene-7,20-cycloveatchan-12-one (3c) exhibited cytotoxicity against HeLa and HEp-2 lines at a concentration of 100 μg/mL. The other songorine derivatives caused dose-dependent proliferation of cancer cells. [ABSTRACT FROM AUTHOR]

Periodontal ligament stem cells (PDLSCs) have broad applications in tissue engineering and regeneration. However, the function of PDLSCs changes in different microenvironments. This study aimed to explore the effects of different developmental stages on the biological characteristics of PDLSCs. Here, PDLSCs were successfully cultured from the periodontal tissues of various groups, including a group with immature roots, a young group with mature roots, and an aging group with mature roots. By comparing the results of the three experimental groups, we found that the donors with immature roots exhibited the best proliferative ability and osteogenic differentiation, whereas the aging group demonstrated the worst proliferation. The trend for adipogenic differentiation was the opposite to that for osteogenic differentiation. The cell sheet and in vivo experiments revealed that in the immature root group, the cells produced more extracellular matrix and new bone and better absorbed the implant materials. These results indicate that PDLSCs perform various functions at different stages of development. In clinical applications of PDLSCs for periodontal regeneration, donors with incompletely developed roots have stronger biological characteristics. [ABSTRACT FROM AUTHOR]

This study delved into the role of delta‐like noncanonical notch ligand 2 (DLK2) in the cell cycle, proliferation, apoptosis, and differentiation of myoblasts, as well as its interaction with the classical Wnt/β‐catenin signaling pathway in regulating myoblast function. The research revealed that upregulation of DLK2 in myoblasts during the proliferation phase enhanced myoblast proliferation, facilitated cell cycle progression, and reduced apoptosis. Conversely, downregulation of DLK2 expression using siRNA during the differentiation phase promoted myoblast hypertrophy and fusion, suppressed the expression of muscle fiber degradation factors, and expedited the differentiation process. DLK2 regulates myoblasts function by influencing the expression of various factors associated with the Wnt/β‐catenin signaling pathway, including CTNNB1, FZD1, FZD6, RSPO1, RSPO4, WNT4, WNT5A, and adenomatous polyposis coli. In essence, DLK2, with the involvement of the Wnt/β‐catenin signaling pathway, plays a crucial regulatory role in the cell cycle, proliferation, apoptosis, and differentiation of myoblasts. [ABSTRACT FROM AUTHOR]

In our previous study, circ_015343 was found to inhibit the viability and proliferation of ovine mammary epithelial cells (OMECs) and the expression levels of milk fat synthesis marker genes, but the regulatory mechanism underlying the processes is still unclear. Accordingly in this study, the target relationships between circ_015343 with miR‐25 and between miR‐25 with insulin induced gene 1 (INSIG1) were verified, and the functions of miR‐25 and INSIG1 were investigated in OMECs. The dual‐luciferase reporter assay revealed that miR‐25 mimic remarkably decreased the luciferase activity of circ_015343 in HEK293T cells cotransfected with a wild‐type vector, while it did not change the activity of circ_015343 in HEK293T cells cotransfected with a mutant vector. These suggest that cic_015343 can adsorb and bind miR‐25. The miR‐25 increased the viability and proliferation of OMECs, and the content of triglycerides in OMECs. In addition, INSIG1 was found to be a target gene of miR‐25 using a dual‐luciferase reporter assay. Overexpression of INSIG1 decreased the viability, proliferation, and level of triglycerides of OMECs. In contrast, the inhibition of INSIG1 in expression had the opposite effect on activities and triglycerides of OMECs with overexpressed INSIG1. A rescue experiment revealed that circ_015343 alleviated the inhibitory effect of miR‐25 on the mRNA and protein abundance of INSIG1. These results indicate that circ_015343 sponges miR‐25 to inhibit the activities and content of triglycerides of OMECs by upregulating the expression of INSIG1 in OMECs. This study provided new insights for understanding the genetic molecular mechanism of lactation traits in sheep. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is the leading cause of cancer death worldwide. LC can be classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), with the last subtype accounting for approximately 85% of all diagnosed lung cancer cases. Despite the existence of different types of treatment for this disease, the development of resistance to therapies and tumor recurrence in patients have maintained the need to find new therapeutic options to combat this pathology, where natural products stand out as an attractive source for this search. Nordihydroguaiaretic acid (NDGA) is the main metabolite extracted from the Larrea tridentata plant and has been shown to have different biological activities, including anticancer activity. In this study, H1975, H1299, and A549 cell lines were treated with NDGA, and its effect on cell viability, proliferation, and metabolism was evaluated using a resazurin reduction assay, incorporation of BrdU, and ki-67 gene expression and glucose uptake measurement, respectively. In addition, the combination of NDGA with clinical chemotherapeutics was investigated using an MTT assay and Combenefit software (version 2.02). The results showed that NDGA decreases the viability and proliferation of NSCLC cells and differentially modulates the expression of genes associated with different metabolic pathways. For example, the LDH gene expression decreased in all cell lines analyzed. However, GLUT3 gene expression increased after 24 h of treatment. The expression of the HIF-1 gene decreased early in the H1299 and A549 cell lines. In addition, the combination of NDGA with three chemotherapeutics (carboplatin, gemcitabine, and taxol) shows a synergic pattern in the decrease of cell viability on the H1299 cell line. In summary, this research provides new evidence about the role of NDGA in lung cancer. Interestingly, using NDGA to enhance the anticancer activity of antitumoral drugs could be an improved therapeutic resource against lung cancer. [ABSTRACT FROM AUTHOR]

A series of differentially expressed circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were identified through sequencing in the hair follicle tissues of Hu sheep with small-waved and straight wool patterns. Based on these findings, the circCSPP1-miR-10a-BMP7 (Bone Morphogenetic Protein 7) regulatory network was constructed. The preliminary study highlighted that miR-10a and the BMP7 gene exhibited not only significant differential expression across hair follicle tissues with different patterns in Hu sheep but also had an impact on the proliferation of hair papilla cells. The proliferation of hair papilla cells is intricately linked to hair follicle development and growth. Consequently, we selected the circCSPP1-miR-10a-BMP7 regulatory network to validate its role in promoting hair papilla cell proliferation in Hu sheep. Firstly, the authenticity of circCSPP1 was successfully confirmed through RNase R digestion and reverse primer amplification. Additionally, nucleoplasmic localization analysis determined that circCSPP1 was predominantly distributed in the cytoplasm. Using the dual-luciferase gene reporter system, we verified the targeting relationship between circCSPP1 and miR-10a, building upon our previous validation of the miR-10a-BMP7 interaction. This clarified the competing endogenous RNA (ceRNA) mechanism within the circCSPP1-miR-10a-BMP7. Furthermore, rescue experiments confirmed that circCSPP1 competitively binds to miR-10a, thereby regulating BMP7 expression and influencing the proliferation of hair papilla cells in Hu sheep. This discovery provides a solid foundation for future investigations into the mechanisms underlying wool curvature and the formation of lambskin patterns, offering insights into the complex regulatory networks that govern these phenotypic traits in Hu sheep. [ABSTRACT FROM AUTHOR]

Glycogen-storing so-called clear cell kidney tubules (CCTs), precursor lesions of renal cell carcinoma, have been described in diabetic rats and in humans. The lesions show upregulation of the Akt/mTOR-pathway and the related transcription factor carbohydrate responsive element binding protein (ChREBP), which is supposedly pro-oncogenic. We investigated the effect of ChREBP-knockout on nephrocarcinogenesis in streptozotocin-induced diabetic and normoglycemic mice. Diabetic, but not non-diabetic mice, showed CCTs at 3, 6 and 12 months of age. Glycogenosis was confirmed by periodic acid schiff reaction and transmission electron microscopy. CCTs in ChREBP-knockout mice consisted of larger cells and occurred more frequently compared to wildtype mice. Progression towards kidney tumors was observed in both diabetic groups but occurred earlier in ChREBP-knockout mice. Proliferative activity assessed by BrdU-labeling was lower in 1-week-old but higher in 12-month-old diabetic ChREBP-knockout mice. Surprisingly, renal neoplasms occurred spontaneously in non-diabetic ChREBP-knockout, but not non-diabetic wildtype mice, indicating an unexpected tumor-suppressive function of ChREBP. Immunohistochemistry showed upregulated glycolysis and lipogenesis, along with activated Akt/mTOR-signaling in tumors of ChREBP-knockout groups. Immunohistochemistry of human clear cell renal cell carcinomas revealed reduced ChREBP expression compared to normal kidney tissue. However, the molecular mechanisms by which loss of ChREBP might facilitate tumorigenesis require further investigation. [ABSTRACT FROM AUTHOR]

The beneficial impact of physical training in lowering cancer risk is well known. However, the precise mechanisms linking physical training and cancer are not fully understood. Skeletal muscle releases various myokines that seem to possess a direct anti-tumor effect. Although breast cancer (BC) is the prevalent form of cancer among women on a global scale, only limited data are available about the secretion of myokines following exercise in patients with BC. To study the effects of exercise on BC, the blood samples of patients with varied stages of BC were analyzed after 12 weeks of resistance training with whole-body electromyostimulation (WB-EMS). Following the training period, we observed that resistance training helps these patients to improve their physical characteristics and performance function by increasing skeletal muscle mass and strengthening their hand grip. Notably, the patient's serum was found to inhibit the growth and promote the apoptosis of BC cells in vitro. Moreover, the conditioned medium collected from in vitro stimulated human myotubes using electric pulse stimulation (EPS), an in vitro simulation of WB-EMS training, induced the cell death of BC cells. These results highlighted the direct cancer-protective effects of activated skeletal muscle. In line with our observed effects of serum from exercise-trained pancreatic and prostate cancer patients, the growth of BC cells was notably inhibited when supplemented directly with recombinant myokines C-X-C motif ligand 1 (CXCL1), Interleukin 10 (IL10), and C-C motif chemokine ligand 4 (CCL4). Notably, treatment with these myokines also increased the expression of caspase 3/7 (Casp3/7), resulting in enhanced BC cell death. Our data strongly suggest that physical exercise has a positive impact on skeletal muscle mass and hand grip strength in BC patients, along with a significant anti-tumor effect in BC cells. This shows promising potential for considering sports and physical training as supportive therapies for achieving more impactful cancer treatment. [ABSTRACT FROM AUTHOR]

The histone variant H2A.Z plays important functions in the regulation of gene expression. In mammals, it is encoded by two genes, giving rise to two highly related isoforms named H2A.Z.1 and H2A.Z.2, which can have similar or antagonistic functions depending on the promoter. Knowledge of the physiopathological consequences of such functions emerges, but how the balance between these isoforms regulates tissue homeostasis is not fully understood. Here, we investigated the relative role of H2A.Z isoforms in intestinal epithelial homeostasis. Through genome-wide analysis of H2A.Z genomic localization in differentiating Caco-2 cells, we uncovered an enrichment of H2A.Z isoforms on the bodies of genes which are induced during enterocyte differentiation, stressing the potential importance of H2A.Z isoforms dynamics in this process. Through a combination of in vitro and in vivo experiments, we further demonstrated the two isoforms cooperate for stem and progenitor cells proliferation, as well as for secretory lineage differentiation. However, we found that they antagonistically regulate enterocyte differentiation, with H2A.Z.1 preventing terminal differentiation and H2A.Z.2 favoring it. Altogether, these data indicate that H2A.Z isoforms are critical regulators of intestine homeostasis and may provide a paradigm of how the balance between two isoforms of the same chromatin structural protein can control physiopathological processes. [ABSTRACT FROM AUTHOR]

Glioblastomas (GBM) are most common types of primary brain tumors and miRNAs play an important role in pathogenesis of glioblastomas. Here, we reported a new miRNA, miR-3154, which regulates glioblastoma proliferation and metastasis. miR-3154 was elevated in glioblastoma tissue and cell lines, and its elevation was associated with grade of glioblastomas. Knockdown of miR-3154 in cell lines weakened ability of proliferation and colony formation, and caused cell cycle arrested and higher percentage of apoptosis. Knockdown of miR-3154 also impaired ability of migration and invasion in glioblastoma cells. In mechanism, miR-3154 bound directly to Tumor Protein P53 Inducible Nuclear Protein 1 (TP53INP1), down-regulating TP53INP1 expression at both mRNA and protein level. Silence of TP53INP1 reversed the effect of miR-3154 knockdown on proliferation and metastasis of glioblastoma cells. These findings show that miR-3154 promotes glioblastoma proliferation and metastasis via targeting TP53INP1. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. DEAD/H‐box helicase 11 (DDX11), a DNA helicase, has been implicated in the progression of several cancers. Yet, the precise function of DDX11 in OSCC is poorly understood. The DDX11 expression in OSCC cells and normal oral keratinocytes was evaluated in the Gene Expression Omnibus database (GSE146483 and GSE31853). SCC‐4 and CAL‐27 cells expressing doxycycline‐inducible DDX11 or DDX11 shRNA were generated by lentiviral infection. The role of DDX11 in OSCC cells was determined by 3‐(4, 5‐Dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay, colony formation assay, flow cytometry assay, TUNEL staining, and western blot. The effects of DDX11 on tumor growth were explored in a xenograft nude mouse model. The relationship between DDX11 and transcription factor Yin Yang‐1 (YY1) was researched using the dual luciferase report assay and chromatin immunoprecipitation assay. DDX11 expression was significantly upregulated in OSCC cells. Knockdown of DDX11 inhibited cell proliferation, induced cell cycle arrest, and suppressed PI3K‐AKT pathway, while DDX11 overexpression showed opposite effects. The number of apoptotic cells was increased in DDX11 silenced cells. DDX11 upregulation or knockdown accelerated or suppressed tumor growth in vivo, respectively. Moreover, the YY1 bound and activated the DDX11 promoter, resulting in increasing DDX11 expression. Forced expression DDX11 reversed the anticancer effects of YY1 silencing on OSCC cells. DDX11 has tumor‐promoting function in OSCC and is transcriptionally regulated by YY1, indicating that DDX11 may serve as a potential target for the OSCC treatment. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is a prevalent malignancy characterized by poor prognosis and high mortality. The role of triggering receptor expressed on myeloid cells-2 (TREM2) in RCC progression has been increasingly recognized, yet its underlying mechanisms remain to be fully elucidated. The aim of the present study was to assess the effects of TREM2 on RCC cells and its potential mechanisms. Lentiviral transfection was used to knockdown and overexpress TREM2 in RCC cells, and the expression level of TREM2 was evaluated using reverse transcription-quantitative PCR. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to assess the proliferation of the RCC cells. Cell migration and invasion was evaluated using the wound healing assay and Transwell assay, respectively. Western blotting was used to assess the expression levels of TREM2, P53, p-P53, P21 and p-P21 in TREM2 knockdown or overexpression RCC cells. The results demonstrated that the expression level of TREM2 was significantly higher in cancer tissues compared with adjacent normal tissues. The results of the CCK-8 and EdU assays demonstrated that knockdown of TREM2 significantly inhibited the proliferation of RCC cells, whilst overexpression of TREM2 enhanced the proliferation of RCC cells. The results of the wound healing and Transwell assay revealed that, compared with the control group, the overexpression of TREM2 significantly increased the migration and invasion of RCC cells, whereas knockdown of TREM2 significantly decreased the migration of RCC cells. In addition, western blotting demonstrated that the phosphorylation levels of P53 and P21 proteins were significantly increased after TREM2 knockdown in RCC cells. In conclusion, TREM2 is highly expressed in RCC tissues and promotes the migration of RCC cells by inhibiting the P53 signaling pathway. The present study provides new insights into the regulatory effect of TREM2 on RCC and further reveals the potential of TREM2 as a therapeutic target for RCC. [ABSTRACT FROM AUTHOR]

Acrylamide is broadly utilized in numerous areas with different purposes including being an additive, flocculating, sealing, dry strength improver and polymerizing agent, and so forth. Furthermore, it forms in certain food products at high temperatures. It poses serious hazard since its readily water‐soluble and very reactive nature. Besides in vivo studies, several in vitro studies with various cell lines are carried out to evaluate its toxicity. However, of these cell line studies, there are no mesothelium or mesothelioma cell lines. To fill this lacuna, we aimed at examining various dose range of acrylamide on SPC212 human mesothelioma cell line. First, we executed MTT and neutral red cytotoxicity tests and ascertained IC50 dose. Next, we performed inverted, light (haematoxylin–eosin and May Grünwald), fluorescent (DAPI) and confocal microscope (AO/EB) analyses as well as immunohistochemistry for Bax, Bcl‐2 and PCNA proteins. As a result, we found IC50 of acrylamide at 2.65 mM. Starting from 3.13 mM of acrylamide dose, a deep decrease in cell proliferation was observed. Particularly in MTT assay, a proliferative action of acrylamide was detected at 0.39 and 0.78 mM, supported with inverted microscope images. In light microscope analysis, several cellular degenerations, including condensed and kidney‐shaped nucleus were evident. In AO/EB staining, cells with apoptotic characteristics augmented dose‐dependently, being upheld by a parallel uptick in Bax and a dimunition in Bcl‐2 staining. Besides, PCNA decreased at IC50 dose of acrylamide. This is the acrylamide‐associated first study conducted on SPC212 mesothelioma cells encompassing advanced morphological analysis. We believe this study to be an incentive for future studies. [ABSTRACT FROM AUTHOR]

Few biomarkers are available for predicting chemotherapeutic response and prognosis in colorectal cancer (CRC). Long‐noncoding RNAs (lncRNAs) are essential for CRC development and growth. Therefore, studying lncRNAs may reveal potential predictors of chemotherapy response and prognosis in CRC. LINC01764 was analyzed using datasets from Fudan University Shanghai Cancer Center's advanced CRC patients' RNA‐seq and The Cancer Genome Atlas datasets. Gene set enrichment analysis was employed to detect related pathways. Cotransfection experiments, RNA pulldown assays, RNA‐binding protein immunoprecipitation, protein synthesis activity, and dual‐luciferase reporter assays were performed to determine interactions among LINC01764, hnRNPK, and c‐MYC. High LINC01764 expression correlates with metastasis, a poor response to FOLFOX/XELOX chemotherapy, and a poor prognosis in CRC. LINC01764 enhance glycolysis and glutamine metabolism to promote CRC cells proliferation, metastasis, and 5‐fluorouracil (5‐FU) resistance. LINC01764 specifically binds to hnRNPK, facilitating its interaction with c‐MYC mRNA and promoting internal ribosome entry site (IRES)‐dependent translation of c‐MYC, thereby exerting oncogenic effects. LINC01764 induced 5‐FU chemoresistance by upregulating the c‐MYC, glucose, and glutamine metabolism pathways, which downregulated UPP1, crucial for activating 5‐FU. Conclusively, LINC01764 promotes CRC progression and 5‐FU resistance through hnRNPK‐mediated‐c‐MYC IRES‐dependent translational regulation, which suggests its potential as a predictor of CRC chemotherapy response and prognosis. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) represents a substantial challenge to public health. Despite extensive research, the pathogenesis of CRC is not yet fully elucidated, hindering the development of effective therapeutic strategies. Recent advancements have underscored the importance of Non‐coding RNAs in tumor biology. Our research identified a significant upregulation of Linc00475 in CRC, which correlated with reduced survival rates among CRC patients. Consequently, this study aimed to elucidate the mechanisms by which Linc00475 contributed to CRC progression. Employing a comprehensive array of experimental techniques—including CCK‐8 assays, colony formation assays, flow cytometry, quantitative PCR (qPCR), western blot analysis, and in vivo tumorigenesis assays—we have demonstrated that Linc00475 enhances CRC cell proliferation. Further analysis revealed that Linc00475 directly interacted with miR‐107, leading to its downregulation. Moreover, our findings confirmed that miR‐107 directly targeted CDK6, which was markedly downregulated following Linc00475 silencing. In vivo experiments further indicated that the silencing of Linc00475 markedly inhibited the proliferation of CRC cells. Collectively, our findings suggested that Linc00475 facilitated CRC cell proliferation through the regulation of the miR‐107/CDK6 axis, thereby providing a novel perspective for understanding the molecular mechanisms underlying CRC development. [ABSTRACT FROM AUTHOR]

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the role of interferon regulatory factor 4 (IRF4) in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and analyze the underlying signaling of these processes. In this study, IRF4 is upregulated in periodontitis periodontal ligament tissues, as compared to healthy periodontal ligament tissues. IRF4 knockdown increases cell proliferation, decreases levels of tumor necrosis factor‐alpha, interleukin‐6, and interleukin‐8, enhances osteogenic activity, and increases the expression of RUNX family transcription factor 2, Collagen I, and Osteocalcin in PDLSCs. The opposite results are observed in IRF4 overexpressed PDLSCs. Additionally, GSEA shows that IRF4 activates the interleukin‐18 (IL‐18) signaling pathway. The expressions of IL‐18, B‐cell translocation gene 2, interleukin‐1beta, and caspase‐3 are decreased by IRF4 knockdown, while increased by IRF4 overexpression. IL‐18 overexpression eliminates the promoting effect of IRF4 knockdown on osteogenic differentiation of PDLSCs. In conclusion, IRF4 suppresses osteogenic differentiation of PDLSCs by activating the IL‐18 signaling pathway. [ABSTRACT FROM AUTHOR]

This study investigates the cytotoxicity of various orthodontic archwires, which are essential in directing tooth movement through biomechanical forces. With advancements in material science, different archwire materials have been developed to balance mechanical performance with aesthetic and biological considerations. The study focuses on evaluating the biocompatibility and mechanical properties of stainless steel, nickel–titanium, and chromium–cobalt archwires, particularly their cytotoxic effects on oral cavity cells. In vitro cell culture experiments with fibroblasts, combined with scanning electron microscopy (SEM) analysis, were conducted to assess cell viability and morphology. The results revealed significant differences in cytotoxicity, with copper wires showing high toxicity and causing extensive cell death, while nickel–titanium and chromium–cobalt wires supported better cell viability and healthier cell morphology. These findings highlight the importance of selecting archwire materials that ensure mechanical efficiency without compromising cellular health, emphasizing the need for ongoing assessment of material biocompatibility in the oral environment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Mesothelioma is an aggressive cancer with limited treatment options. Mesothelioma therapy often involves a multimodal approach including surgery, radiotherapy and chemotherapy. However, the prognosis for patients remains poor. Difficult diagnosis, late symptoms when the tumor is in an advanced stage and the onset of chemotherapy resistance make mesothelioma difficult to treat. For this reason, it is essential to discover new pharmacological approaches. Capsaicin (CAPS) is the active compound of chili peppers. Based on CAPS's anticancer properties on various tumor lines and its chemo-sensitizing action on resistant cells, in this study, we evaluated the effects of CAPS on mesothelioma cells to assess its potential use in mesothelioma therapy. Methods: To evaluate antiproliferative effects of CAPS, we performed MTS assays on various mesothelioma cells, representative of all major mesothelioma subtypes. Transwell migration and wound-healing assays were used to examine the effect of CAPS on mesothelioma cell migration. We also determined the effects of CAPS on oncogenic signaling pathways by assessing the levels of AKT and MAPK activation. Results: In this study, we show that CAPS significantly reduces proliferation of both parental and cisplatin-resistant mesothelioma cells. CAPS promotes S-phase cell cycle arrest and inhibits lateral motility and migration of mesothelioma cells. Accordingly, CAPS suppresses AKT and ERK1/2 activation in MSTO-211H and NCI-H2052 cells. Our results support an antitumor effect of CAPS on cisplatin-resistant mesothelioma cells, suggesting that it may reduce resistance to cisplatin. Conclusions: Our results could pave the way for further studies to evaluate the use of CAPS for mesothelioma treatment. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) is the primary inducer of cancer‐related death worldwide. Asiaticoside (ATS) is a triterpenoid saponin that has been indicated to possess an antitumor activity in several malignancies. Nonetheless, its detailed functions in NSCLC remain unclarified. In this study, NSCLC cells were exposed to various doses of ATS. Functional experiments were employed to estimate the ATS effect on NSCLC cell behaviors. Western blotting was implemented for protein expression evaluation. A xenograft mouse model was established to assess the ATS effect on NSCLC in vivo. The results showed that ATS restrained NSCLC cell proliferation, cell cycle progression, migration, and invasiveness. ATS reversed TGF‐β‐induced promotion in epithelial‐mesenchymal transition (EMT). Mechanistically, ATS inhibited Wnt/β‐catenin signaling in NSCLC. Upregulating β‐catenin restored ATS‐mediated suppression of NSCLC cell aggressiveness. Moreover, ATS administration repressed tumorigenesis in tumor‐bearing mice. In conclusion, ATS represses growth and metastasis in NSCLC by blocking EMT via the inhibition of Wnt/β‐catenin signaling. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the efficacy of Ginsenoside Rg3 on the reproduction and immigration of HCT-116 cells and its molecular mechanism. Methods: Analysis of the cell cycle along with the colony formation assay, and MTT test were performed to detect the effect of Ginsenoside Rg3 (GRg3) on proliferation of HCT-116 cells. Transwell assay and Cell scratch wound method were carried out to determine the impact on the immigration. The differential expressed genes obtained by RNA-sequencing were intersected with the predicted target genes of GRg3, and PPI was constructed to analyze hub genes. The key target gene expression and its downstream genes were evaluated by western blot assay. Results: The GRg3 can inhibit the reproduction and immigrating ability of colonic carcinoma cells, decrease the ability of colony formation in HCT-116 cells, and arrest the G2 phase. JAK3 was identified as a key target gene. Western blot assay revealed decreased levels of p-STAT5 and JAK3 post-treatment with RG3, while STAT5a and STAT5b did not change significantly. Conclusion: The GRg3 inhibits the phosphorylation of STAT5 but not the expression of total protein by inhibiting the expression of JAK3, and then inhibits the proliferation and migration of HCT-116 cells. [ABSTRACT FROM AUTHOR]

Radial glia (RG) are the main progenitor cell type in the developing cortex. These cells are highly polarized, with a long basal process spanning the entire thickness of the cortex and acting as a support for neuronal migration. The RG cell terminates by an endfoot that contacts the pial (basal) surface. A shorter apical process also terminates with an endfoot that faces the ventricle, with a primary cilium protruding in the cerebrospinal fluid. These cell domains have particular subcellular compositions that are critical for the correct functioning of RG. When altered, this can affect proper development of the cortex, ultimately leading to cortical malformations, associated with different pathological outcomes. In this review, we focus on the current knowledge concerning the cell biology of these bipolar stem cells and discuss the role of their polarity in health and disease. [ABSTRACT FROM AUTHOR]

Objective: This study employs integrated bioinformatics analysis and in vitro cellular experiments to elucidate the role of Synaptotagmin-12 (SYT12) in the progression of gastric cancer. Methods: We utilized databases and platforms such as Xiantao Academic Tools, UALCAN, Kaplan-Meier plotter analysis, and The Cancer Genome Atlas (TCGA) to extract datasets on SYT12 in gastric cancer. We analyzed the relationship between SYT12 expression and the clinicopathological features, prognosis, diagnosis, and immune infiltration of stomach adenocarcinoma (STAD) patients. Verification was conducted using samples from 31 gastric cancer patients. Additionally, in vitro cellular experiments were performed to determine the role and potential mechanisms of SYT12 in the malignant behavior of gastric cancer cells. Results: Comprehensive bioinformatics analysis indicated that SYT12 is highly expressed in most cancers and is associated with promoter DeoxyriboNucleic Acid (DNA) methylation levels. SYT12 expression correlated with clinicopathological features, immune cell infiltration, immune checkpoint gene expression, and poor prognosis in STAD patients. In vitro experiments suggest that SYT12 may promote the proliferation and migration of gastric cancer cells by inducing epithelial-mesenchymal transition (EMT). Conclusions: This study highlights the significant role of SYT12 in gastric cancer, suggesting its potential as a new target for early diagnosis, treatment, immunological, and prognostic evaluation in gastric cancer, offering new insights for precision medicine in this disease. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer, a subtype of breast cancer, is characterized by a poor prognosis. Recent studies have shown that miRNA30b acts as an oncogene and is vital for the proliferation of malignancies across various systems. This study aimed to elucidate the impact of miRNA30b on the proliferation, migration, and invasion capabilities of breast cancer cells in vitro. Methods: Triple‐negative breast cancer cell lines MDA‐MB‐231 were transiently transfected with miRNA30b inhibitor, mimic, or the negative control by Lipofectamine 2000. Successful transfection was confirmed by quantitative real‐time polymerase chain reaction (qRT‐PCR). Functional assays, including CCK8, clone formation, scratch, and transwell assays, were conducted to evaluate the proliferation, invasion, and migration ability of MDA‐MB‐231 cells in each group. The target protein of miRNA30b was determined using an online prediction data website, and the dual‐luciferase assay confirmed whether there was a binding site between miRNA30b and ADAM12. The effect was further verified by Western blot analysis. Results: MDA‐MB‐231 cells were transfected with miRNA30b inhibitor, mimic, and negative control. miRNA30b expression was downregulated in the cells. Relative to the negative control group, miRNA30b expression significantly increased in the mimic group and decreased in the miRNA30b inhibitor group, with the differences being statistically significant. The miRNA30b mimic group exhibited a significant increase in miRNA30b expression and a corresponding promotion of cell proliferation, colony formation, and migration. Conversely, the miRNA30b inhibitor group displayed significantly reduced miRNA30b expression and suppressed cell proliferation, colony formation, and migration abilities compared to the negative control cells. Bioinformatics software predicted ADAM12 as a potential target of miRNA30b. Dual‐luciferase assays confirmed the presence of a binding site between miRNA30b and ADAM12. Western blot analysis revealed that overexpression of miRNA30b downregulated ADAM12 expression in MDA‐MB‐231 cells. Conclusions: miRNA30b could promote proliferation, migration, and invasion of TNBC cell lines MDA‐MB‐231. The effect of miRNA30b on triple‐negative breast cancer would be achieved partly at least through inhibiting the expression of ADAM12. [ABSTRACT FROM AUTHOR]

ABSTRACT UVA radiation, a primary risk factor in melanoma progression, partly acts through the mediation of reactive oxygen species (ROS). The role of ROS in driving cutaneous melanoma toward an invasive phenotype and whether it occurs through opsins (OPNs), which are photosensitive G protein‐coupled receptors, is not fully understood. This study focuses on the impact of UVA radiation on melanoma cell proliferation, with a special emphasis on OPN3. Investigating the biphasic response to various UVA doses (0.75–9 J/cm2) in A375 and MV3 cell lines, and using EdU and CCK‐8 assays, we observed dose‐dependent changes in cell proliferation. Interestingly, UVA irradiation at these doses of 0.75, 1.5 and 3 J/cm2 did not significantly induce ROS production. Our study further delves into the role of OPN3, a photosensitive receptor, in melanoma progression. Following UVA exposure, an increase in OPN3 expression was observed in melanoma cells lines A375 and MV3, indicating its role as a UVA‐sensitive sensor and its influence on cell proliferation. Additionally, UVA‐induced calcium flux in two melanoma cells lines pointed to a calcium‐dependent G protein‐coupled pathway in melanoma proliferation, mediated by OPN3 and not reliant on ROS. This research sheds light on the mechanism of UVA‐induced melanoma progression, underscoring OPN3 as a pivotal regulator and advancing our understanding of UVA's interaction with opsins in melanoma progression. [ABSTRACT FROM AUTHOR]

Background: To explore the association of long non-coding RNA (lncRNA) SNHG1/ miR-195 axis with type 2 diabetes mellitus (T2DM) and islet function. Methods: The expression of SNHG1 and miR-195 was measured in T2DM patients and in healthy subjects. Correlation between indciators was evaluated using Pearson correlation analysis. INS-1 cells were used to perform the cell function assays. Insulin secretion by INS-1 was detected using ELISA. Cell counting kit-8 (CCK-8) and flow cytometry was used to detect cell proliferation and apoptosis. Luciferase report assay was to used to verify the target of SNHG1. Results: The expression of SNHG1 was increased and miR-195 level was decreased in the serum of T2DM patients. Both SNHG1 and miR-195 could be biomarkers for T2DM diagnosis. The fasting plasma glucose (FPG) and HbA1c were positively related to SNHG1 and negatively related to miR-195. SNHG1 inhibited insulin secretion, and cell proliferation and promoted apoptosis of INS-1 cells via binding to miR-195. Conclusions: Detection of SNHG1 and miR-195 might predict T2DM. SNHG1 could suppress proliferation and insulin secretion, but promote apoptosis of INS-1 cells via sponging miR-195. [ABSTRACT FROM AUTHOR]

Background: Propionic acid (PA) is an intermediate product of metabolism of intestinal bacteria and may protect the intestinal barrier from disruption. The aim of the study was to investigate the apoptotic and proliferative processes in the small intestine (SI) of rats with type 2 diabetes mellitus (T2DM) on the background of metformin monotherapy and its combination with PA. Methods: Male Wistar rats were divided: 1) control; 2) T2DM (3-month high-fat diet followed by streptozotocin injection of 25 mg/kg of body weight); 3) T2DM + metformin (60 mg/kg, 14 days, orally); 4) T2DM + PA (60 mg/kg, 14 days, orally); 5) T2DM + PA + metformin. Western blotting, RT-PCR, and scanning electron microscopy were performed. Results: We observed profound changes in the SI of diabetic rats suggesting the disturbed intestinal homeostasis: impaired mitochondrial ultrastructure, increased cristae volume, and decreased content of proliferative marker Ki67 with almost unchanged proapoptotic caspase-3 and its p17 subunit levels. Metformin and PA monotherapies also led to an increased cristae volume, however, after their combination, a tendency to normalization of ultrastructure of mitochondria was observed. While there was a significant inhibition of proliferation in T2DM and, in greater extent, after metformin and PA monotherapies, differential influence on apoptosis in the SI was observed. While metformin inhibited apoptosis via Bax declining, PA mainly acted via caspase-3-dependent mechanism elevating its active p17 subunit. Conclusion: PA supplementation for the improvement of diabetes-induced gastrointestinal complications concurrently with metformin may be consider as a perspective supportive therapy. Data related to PA action on SI may be valuable during the development of new treatment strategies for diabetes induced intestinal disturbances raised after metformin treatment. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)‐induced psoriasis like‐dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ‐induced psoriasis model alleviates psoriasis‐like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of β‐Trcp to MDM2. This interaction inhibits β‐Trcp‐induced‐K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors, with high incidence and poor prognosis. Revealing mechanisms of ESCC progression and developing new therapeutic targets remains crucial. The aim of this study was to elucidate the molecular mechanism of miR‐30c‐5p in regulating the malignant progression of ESCC. Methods: TCGA, GEO, and other datasets were used to analyze the differential expression of miR‐30c‐5p in ESCC and adjacent tissues, and its impact on prognosis. Then the effects of miR‐30c‐5p on the proliferation, migration, and invasion of TE‐1 and Eca9706 cells were investigated through proliferation experiments, transwell and wounding healing assays. The regulatory mechanism of miR‐30c‐5p on the PI3K/AKT signaling pathway and its interaction in cancer progression were investigated through Western blots, dual‐luciferase reporter assay, and rescue experiments. Results: miR‐30c‐5p was significantly downregulated in ESCC tissue and represented a poor prognosis. miR‐30c‐5p mimic significantly inhibited the proliferation, migration, and invasion ability of ESCC, while miR‐30c‐5p inhibitor significantly promoted tumor cell progression. Through bioinformatic analysis and experimental results, miR‐30c‐5p interacted directly with PIK3CA mRNA and inhibited subsequent signaling pathway activation. PIK3CA activator could eliminate the inhibitory effects of miR‐30c‐5p mimic on the progression of ESCC, while PIK3CA inhibitors could rescue the promoting effect of miR‐30c‐5p inhibitor group cells. Conclusions: In summary, we found that miR‐30c‐5p inhibited the proliferation, invasion and migration of ESCC by inhibiting PI3K/AKT signaling pathway for the first time, and this study is expected to provide a novel insight and potential therapeutic target for managing ESCC. [ABSTRACT FROM AUTHOR]