Cytojournal最新文献

Objective: Epilepsy is a neurological disease whose onset causes a variety of sequelae, reducing the standard of living. TWIK-related K⁺ channel 1 (TREK-1) has been linked to epilepsy. C-X-C motif chemokine receptor (CXCR2) is a potential target for the treatment of epilepsy inflammation. This work aims to observe the effect of CXCR2 expression on neuron autophagy and TREK-1 expression in the hippocampus of epileptic mice.

Material and methods: An animal model of epilepsy was established, and the CXCR2 gene was silenced. The expression of TREK-1, interleukin (IL)-1b, tumor necrosis factor-a, and IL-6 in the hippocampus of mice was detected by quantitative real-time polymerase chain reaction. Autophagy-related proteins beclin-1 and microtubule-associated protein light chain 3 (LC3) were examined by Western blot. Cell proliferation and activity were analyzed using cell counting kit-8 and 5-Bromodeoxyuridine assays.

Results: Compared with that in the normal group, TREK-1 expression decreased and CXCR2 expression increased significantly in the hippocampus of epileptic model mice (P < 0.01). Two autophagy markers, beclin-1 and LC3 II/LC3 I, showed an increased expression in the hippocampal regions of the epileptic model group (P < 0.01). In addition, B-cell lymphoma 2 (Bcl-2)-associated X protein levels increased and Bcl-2 levels decreased in the epileptic mice (P < 0.01). After CXCR2 silencing, the expression of proinflammatory factor in the hippocampus of epileptic mice significantly decreased (P < 0.01). In vitro, cell viability and proliferation increased significantly after silencing CXCR2 (P < 0.05). Meanwhile, the expression levels of TREK-1 and Bcl-2 significantly increased (P < 0.001) and the levels of autophagy markers decreased in vivo and in vitro (P < 0.01). In vivo, CXCR2 expression did not change significantly after silencing TREK-1. After silencing TREK-1 and overexpressing CXCR2, the proliferation ability of HT22 cells decreased significantly (P < 0.001).

Conclusion: Epileptic mice's hippocampal neuronal damage can be ameliorated by CXCR2 suppression. One possible explanation is that epileptic mice's hippocampus tissues express more TREK-1, which prevents excessive neuronal autophagy and lowers apoptosis.

Objective: Lung adenocarcinoma is a type of lung cancer that falls under the category of non-small cell carcinoma. Given its high incidence, it has attracted considerable attention. Zinc finger TRAF-type containing 1 (ZFTRAF1) was found in a two-hybrid yeast screening with muine galectin-3. However, the link between ZFTRAF1 and lung adenocarcinoma was unclear. This study aimed to explore the influencing mechanism of ZFTRAF1 on lung adenocarcinoma.

Material and methods: In this study, by silencing or overexpressing ZFTRAF1, we investigated the migration and invasion ability of A549 and HCC827 cells. In addition, the polarization effect of ZFTRAF1 on macrophages was evaluated through flow cytometry and quantitative real-time polymerase chain reaction. Finally, tumor growth and development were evaluated through histological analysis in vivo and Western Blot analysis in vitro.

Results: ZFTRAF1 was down-regulated in normal lung cells. Silencing of ZFTRAF1 inhibited migration, invasion of A549 and HCC827 cells, and the formation of tumors. Reduction of the expression of ZFTRAF1 inhibited the epithelial-mesenchymal transition, suppressed the phosphoinositide 3-kinase-protein kinase B pathway, and enhanced the polarization of M1 macrophages. In addition, the overexpression of ZFTRAF1 showed an opposite trend compared with its silencing in A549 and HCC827 cells.

Conclusion: ZFTRAF1 promotes lung cancer development. Regulating the expression level of ZFTRAF1 to interfere with the growth and migration of lung adenocarcinoma may be a new strategy for the treatment of lung adenocarcinoma. In addition, the theoretical foundation for ZFTRAF1's therapeutic use is provided in this work.

Objective: Integrin β1 (ITGB1) reportedly participates in osteoblast differentiation, mineralization, and migration. Nevertheless, its role and underlying mechanism in osteoblast differentiation and migration during acute bone loss after fracture are not yet clear. This research was designed to measure the role of ITGB1 in osteoblast differentiation and migration and the underlying mechanism.

Material and methods: ITGB1 expression was assessed in MC3T3-E1 cells at different incubation times (0, 4, 7, 14, 21, and 28 days) through quantitative real-time polymerase chain reaction. Alkaline phosphatase (ALP) activity determination, ALP staining, and Alizarin red staining were performed to evaluate the differentiation degree of osteoblasts. Western blot was performed to detect the expression of markers related to osteoblast differentiation. Osteoblast migration ability was determined by wound healing and transwell assays. The molecular mechanism by which ITGB1 modulated the differentiation and migration of osteoblasts was examined by Western blot.

Results: ITGB1 expression increased significantly after 14, 21, and 28 days of osteoblast differentiation. ITGB1 increases enhanced osteoblast differentiation and migration; conversely, reduced ITGB1 inhibits osteoblast differentiation and migration. Mechanically, ITGB1 facilitated the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, and the suppression of the ERK ERK1/2 pathway attenuated the effects of ITGB1 on osteoblast differentiation and migration.

Conclusion: ITGB1 plays an important role in osteoblast differentiation and migration by activating the ERK1/2 signaling pathway, which may provide novel insights into bone injury treatment.

Objective: Non-small-cell lung cancer (NSCLC) is one of the most frequently occurring and aggressive cancers globally, but its complex molecular mechanisms remain only partially understood. This study investigated the effects of Wilms tumor 1-associated protein (WTAP) on NSCLC cell ferroptosis and immune escape through N6-methyladenosine (m6A) modification of twist family BHLH transcription factor 1 (Twist1).

Material and methods: Western blot and reverse transcription-quantitative polymerase chain reaction were used to assess Twist1 expression in NSCLC cell lines and its circular structure. Small interfering RNAs targeting Twist1 and WTAP were transfected into H2170 cells, and their effects on cell viability, apoptosis, ferroptosis markers (reactive oxygen species [ROS], malondialdehyde [MDA], and Fe²⁺), and immune escape were evaluated using cell counting kit-8, flow cytometry, terminal deoxynucleotidyl transferase dUTP Nick-End labeling, ROS staining, and enzyme-linked immunosorbent assay. Co-culture with CD8⁺ T cells was employed to assess cytotoxicity and exhaustion marker expression (Lymphocyte activation gene-3, Programmed cell death protein 1, and T-cell immunoreceptor with Ig and ITIM domains). Magna methylated RNA immunoprecipitation, photo-activatable ribonucleoside-enhanced cross-linking and immunoprecipitation, and treatment with the methylation inhibitor 3-Deazaneplanocin A (3-DAA) confirmed the m6A modification of Twist1 and WTAP's regulatory role.

Results: Twist1 was dramatically elevated in the NSCLC cell lines (P < 0.05). Knockdown of Twist1 inhibited NSCLC cell viability; promoted apoptosis; increased ROS, MDA, and Fe²⁺ levels; enhanced the cytotoxicity of CD8⁺ T cells; and reduced the expression of exhaustion markers (P < 0.05). These effects were partially reversed by the ferroptosis inhibitor Fer-1. WTAP expression increased in the NSCLC cells, and its knockdown markedly reduced the m6A modification and expression of Twist1 (P < 0.05). Furthermore, overexpression of Twist1 partially reversed the inhibitory effects of WTAP knockdown on NSCLC cell proliferation, ferroptosis, and immune escape (P < 0.05).

Conclusion: Twist1 is highly expressed in NSCLC. It promotes NSCLC progression by enhancing ferroptosis and immune escape. WTAP-mediated m6A methylation plays a critical role in regulating Twist1 expression. The WTAP/Twist1 axis may serve as a potential therapeutic target for NSCLC.

Objective: The liver is a common primary cancer site in humans. Actin-related protein 6 (ACTR6) plays a key role in liver cancer. The aim of this study was to further explore the regulatory molecular mechanism of ACTR6 in liver cancer.

Material and methods: In this study, hepatoma cell HuH-7 was evaluated by 5-ethynyl-2'-deoxyuridine staining, colony formation, Transwell assay, and wound healing assay. The possible mechanism of the action of ACTR6 on hepatocellular carcinoma cells was evaluated by analyzing sphere formation, the key factors of the Hedgehog (Hh) signaling pathway, and molecules related to cell stemness. Then, xenografted mouse tumor models were used to demonstrate the promotion effect of ACTR6 on liver cancer in vivo.

Results: ACTR6 was highly expressed in HuH-7h and HepG2 cells (P < 0.001). Silencing ACTR6 inhibited the migration, invasion capacity, and activity of HuH-7 (P < 0.01). ACTR6 activated the Hh signaling pathway by upregulating the expression of Sonic Hedgehog, patched 1, smoothened, and glioma-associated transcription factor 1. In addition, ACTR6 increased the molecular level of cell stemness by increasing the level of cellular myelocytomatosis oncogene, octamer-binding transcription factor 4, Nanog homeobox, and SRY-box transcription factor 2. Vismodegib reversed the promoting effect of ACTR6 on the Hh signaling pathway and stem-related proteins in cells.

Conclusion: ACTR6 regulates the molecular basis of stemness maintenance of liver cancer cells through the Hh signaling pathway and promotes the occurrence of liver cancer. This study provides possible targets for the clinical treatment of liver cancer.

Biobanks are essential infrastructures dedicated to the systematic collection, processing, storage, and distribution of biological samples and related data, serving as fundamental resources for biomedical research. Their application ranges from clinical research and epidemiological investigations to public health monitoring, facilitating the identification of disease-associated genetic variations and the exploration of gene-environment interactions. Biobanks provide valuable resources for systems biology and interdisciplinary research, significantly broadening the scope and depth of scientific inquiry. This review explores the development history, current landscape, and future prospects of global biobanking initiatives, highlighting notable advancements in technological innovation and methodological practices. It also scrutinizes prevailing challenges and envisions future trajectories for development. In the era of personalized medicine, biobanks are expected to play a more critical role by providing the data and samples needed for the development of individualized therapies. By surmounting existing impediments and fostering international collaboration, biobanks are poised to propel scientific breakthroughs and elevate global healthcare standards. This article aims to comprehensively elucidate the trajectory of biobanking development and its profound influence on biomedical research.

Objective: Treating triple-negative breast cancer (TNBC) is a major challenge owing to its unique biological characteristics. This study aimed to elucidate the molecular interaction between microRNA-15a-5p and T-cell immunoreceptor associated with immunoglobulin and ITIM domains (TIGIT) in TNBC.

Material and methods: The GSE22513 microarray dataset was subjected to bioinformatic analysis. MDA-MB-231 and MDA-MB-468 cells were transfected with lentiviral constructs for overexpressing TIGIT and microRNA (miRNA) mimics for overexpressing miR-15a-5p. Western blot and quantitative real-time polymerase chain reaction analyses were conducted to quantify TIGIT and miR-15a-5p levels of pre- and post-transfection. Cell proliferation, migration, invasiveness, cell cycle distribution, and apoptosis were assessed using cell counting kit-8, wound-healing, colony formation, transwell assays, and flow cytometry, respectively.

Results: This study identified 139 genes (37 upregulated and 102 downregulated genes). Elevated TIGIT levels exhibited a significant link to unfavorable outcomes in individuals with breast cancer (BC). Additional analyses demonstrated that TIGIT expression in BC cell lines was substantially increased compared with that in normal breast cells. Overexpressing miR-15a-5p effectively inhibited TIGIT expression and consequently suppressed TNBC cell proliferation, invasion, and migration. This inhibition prompted G2/M phase accumulation and enhanced cellular mortality.

Conclusion: miR-15a-5p exerts tumor-suppressive effects through TIGIT downregulation, thereby mitigating the malignant phenotype of TNBC.

Objective: Gastric cancer (GC) persists as a leading global cause of cancer-related mortality. Although bortezomib (BTZ), a proteasome inhibitor, has demonstrated efficacy in treating various cancers, its therapeutic potential is hindered by drug resistance in GC. This study aims to explore the regulatory role of tripartite motif-containing protein 28 (TRIM28) in BTZ resistance in GC cells and to evaluate the antitumor effect of targeting TRIM28 in combination with BTZ.

Material and methods: We established control groups (including Lenti-control and short hairpin non-targeting control groups), TRIM28-overexpressing (OE), and TRIM28-knockdown models using the MGC-803 gastric cancer cell line to investigate TRIM28-mediated BTZ resistance. A series of assays was performed, including cell counting kit-8 analysis to assess cell viability, flow cytometry for apoptosis analysis, colony formation assays to evaluate cell proliferation, western blot to measure the protein expression of 20S proteasome subunits (α1/4 and β1/2/5), proteasome activity assays, and immunohistochemistry to assess TRIM28 expression in clinical samples. Bioinformatic tools were also used to analyze the clinical correlation of TRIM28 expression with cancer stage and grade.

Results: Our results demonstrate that TRIM28 markedly enhanced BTZ resistance in GC cells. TRIM28 OE increased cell viability, inhibited apoptosis, enhanced colony-forming ability, upregulated the expression of proteasome subunits, and increased proteasome activity, contributing to a protective effect against BTZ-induced cytotoxicity. For the clinical GC samples, TRIM28 was highly expressed in tumor tissues, and its expression was correlated with advanced cancer stages and high tumor grades.

Conclusion: TRIM28 is critical in promoting BTZ resistance in GC cells. Targeting TRIM28 could potentiate BTZ treatment outcomes and offer a promising therapeutic strategy for overcoming drug resistance in GC treatment.

Objective: Arthritis is a common chronic disease. The T cell subpopulation, as a key element in the immune system, plays a crucial role in arthritis. This work aimed to explore the involvement of melanocortin 1 receptor (MC1R) in collagen-induced arthritis (CIA) and how it affects the balance of proinflammatory and anti-inflammatory T cell subsets.

Material and methods: Using flow cytometry, the ratios of T helper (Th)1, Th17, and regulatory T (Treg) cells were examined. Using the enzyme-linked immunosorbent assay, pro-interleukin (IL)-17, interferon (IFN)-g, anti-IL-10, and IL-4 were measured.

Results: MC1R knockout (MC1R-KO) mice exhibited an increase in the proportion of Th1 and Th17 cells compared with wild-type mice. The proportion of Treg cells in MC1R-KO mice was reduced. The levels of IL-17 and IFN-g in MC1R-KO mice increased, whereas those of IL-10 and IL-4 decreased.

Conclusion: MC1R-KO mice exacerbated CIA by upregulating the numbers of Th1 and Th17 cells and decreasing the proportion of Treg cells. The increased production of IL-17 and IFN-g, along with the reduced IL-10 and IL-4 levels, further contributed to the enhanced inflammatory response. These findings suggest that MC1R plays a crucial role in the regulation of immune responses and inflammation in CIA. Targeting MC1R may have therapeutic potential for autoimmune diseases characterized by dysregulated T cell subsets.