Cell Journal最新文献

This study aimed to comprehensively review the global biobanks to visualize their geographical distribution. The protocol for this review consisted of the following steps: i. Developing a search strategy to identify biobanks from each continent, ii. Defining variables (such as tissue-based, cell-based, and gene-based biobanks) and organizing them in Excel sheets for data collection, iii. Collecting data, iv. Removing duplicate and invalid entries, v. Structuring the database, and vi. Analyzing the data. MATLAB software was utilized for data analysis and chart plotting. Data on global biobanks aimed to collected through targeted searches of databases, publications, and registries using predefined variables such as biobank type, location, and accessibility. The data were organized, cleaned to remove duplicates, and analyzed using MATLAB to visualize geographical distribution and prevalence patterns. Tissue and cell-based, tissue-based, and cellbased biobanks were the most common type of global biobanks with a prevalence of 30.4, 27.93, and 25.15%. United Kingdom (n=78, P=43.09%), Canada (n=43, P=23.75%), and the United States (n=33, P=18.23%) were the countries with a higher frequency of tissue-based biobanks (domain frequency: 1-78; 0.55-43.09%). However, tissue and genebased biobanks had the most minor frequency and were only in two countries of Spain (n=1, P=25%) and the United Kingdom (n=3, P=75%). The results of this study indicate that the feasibility of designing and conducting biobanks varies by type. Tissue and cell-based biobanks were found to be more prevalent, followed by tissue-based, cell-based, cell and gene-based, tissue, cell, and gene-based, gene-based, and finally, tissue and gene-based biobanks. This study represents the initial step in creating a global database by identifying all types of biobanks worldwide.

Objective: The aim of this study was to understand the interactions between tumor-associated mesenchymal stem cells (TA-MSCs) and triple-negative breast cancer (TNBC) cells, which appear to be necessary for developing effective therapies.

Materials and methods: In this experimental study, MDA-MB-231 and 4T1 TNBC cells were co-cultured with bone marrow-derived MSCs, and TA-MSCs conditioned media (CM) were collected. TA-MSC CM-treated TNBC cells were subjected to migration and invasion assays. Epithelial-mesenchymal transition (EMT) marker expression was quantified by real-time polymerase chain reaction (RT-PCR). Cell proliferation was measured using trypan blue exclusion technique, while cell cycle distribution and apoptosis were assessed by flow cytometry. The effects of TA-MSCs on tumor volume, survival rate, and lung metastasis were evaluated by subcutaneous co-injection of MSCs with 4T1 cells in the right flanks of BALB/c mice (n=5 per group). Intratumoral interleukin-12 (IL-12) immunotherapy was performed using lentiviral particles as a rescue experiment. The TA-MSCs RNA-seq dataset (PRJEB27694) was analyzed to detect elevated metastasis-associated oncogenes, downloaded from the European Nucleotide Archive database. For validation of the RNA-seq data analysis, the expression levels of candidate oncogenes were evaluated in TA-MSCs, TNBC cells, and tumor tissue using RT-PCR.

Results: TA-MSCs enhanced migration, invasion, and EMT of TNBC cells in vitro without affecting cell proliferation or apoptosis. In vivo, TA-MSCs increased tumor growth and lung metastasis, while decreasing survival rates. IL-12 therapy elevated serum IL-12 and interferon-gamma (IFN-γ) expression, suppressed tumor volume and lung metastasis, and improved overall survival in the TA-MSC group. RNA-seq data analysis identified upregulated oncogenes in TA-MSCs, among which MMP3, CXCL2, CXCL5, and ICAM1 were selected as the most relevant to metastasis. These genes showed increased expression in TA-MSCs, TNBC cells, and tumor tissues.

Conclusion: The findings of the present study revealed a complex interplay between TA-MSCs and TNBC cells that affects tumor growth and metastasis. Preclinical results indicate that intratumoral IL-12 immunotherapy shows promise in overcoming TA-MSC-promoted tumor growth and metastasis.

Objective: Quercetin and exercise both have antidiabetic effects through decreasing blood glucose while increasing insulin sensitivity. Therefore, the present study aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercises along with quercetin administration on apoptosis and cardiomyopathy in diabetic obese rats.

Materials and methods: In this experimental study, 35 male Wistar rats [diabetic rats for experimental groups and normal rats for healthy control (HC)] were divided into seven groups (for each group n=5): HC, diabetic control (DC), diabetic quercetin control (DQC), diabetic HIIT (DHT), diabetic MICT (DMT), DHT with quercetin (DQHT) and DMT with quercetin (DQMT). The rats were fed a high-fat diet (HFD) for 8 weeks and a low dose of streptozotocin (STZ) was administered to create a model of type 2 diabetes mellitus (T2DM). Eight weeks of HIIT and MICT with or without quercetin treatment were performed. Quercetin was used at 15 mg/kg, as a suspension in carboxymethyl cellulose (CMC) at a concentration of 0.5%. One-way analysis of variance with LSD's post-hoc test with a significant level of P≤0.05 was used to analyze data.

Results: Just 8 weeks of HIIT and MICT protected the protein content of PI3K, AKT, and FOXO3 and caspase-8 (Casp- 8) gene expression in heart tissues (P<0.05). Quercetin and both training protocols decreased blood glucose, while improving inflammatory markers and the lipid profile (P<0.05).

Conclusion: Reduction in blood glucose along with improvements in the inflammatory markers and the lipid profile by quercetin injection may be a promising approach for the development of new antidiabetic medications. In addition, both training protocols showed potentially successful diabetic cardiomyopathy treatments through modulating the FOXO3 and PI3K/AKT pathways.

Objective: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Engineered biomolecules can be used as a targeted tool to deliver drugs directly to tumors that reduce the adverse effects of conventional treatments. We aimed to prepare non-targeted oxaliplatin-loaded chitosan nanoparticles (OXPT-CS NPs) and targeted OXPT-CS NPs decorated with cetuximab single-chain variable fragment (scFv) to send both NPs to epidermal growth factor receptor (EGFR) overexpressing HCT 116 cells, a human colorectal carcinoma cell line, for comparing their cytotoxicity.

Materials and methods: In this experimental study, OXPT-CS NPs were synthesized using a fluid system. Encapsulation efficiency percentage (EE%) and oxaliplatin release rate were evaluated. Western blot and cell-based ELISA confirmed scFv production and its binding ability to EGFR, respectively. The Fourier transform infrared spectroscopy (FTIR) determined the conjugation of scFv to OXPT-CS NPs. The NPs were characterized, and their toxicity against the HCT 116 cells was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and flow cytometry assays.

Results: The EE% of OXPT-CS NPs was 93%, and the average diameters were 75.85 ± 8.81 nm and 92.48 ± 9.51 before and after scFv conjugation, respectively. The scFv was purified via affinity chromatography. The western blot method and cell-based ELISA revealed successful purification of scFv and its attachment to EGFR on HCT 116 cells. The FTIR analysis determined the interactions between the scFv and OXPT-CS NPs. According to MTT and flow cytometry results, the targeted delivery system significantly reduced HCT 116 cancer cell viability and increased apoptosis induction up to 99.8%.

Conclusion: The scFv-OXPT-CS NPs demonstrated an increased cytotoxic function due to the presence of scFv in its formulation. This delivery system offers a promising method for delivering chemotherapy drugs to cancer cells. More research is needed on the best strategies for improving treatment efficacy by targeting cancer cells.

Cell-based therapy has shown promising outcomes in the treatment of cerebral palsy (CP). However, there is no consensus on a standard therapeutic protocol regarding the source of cells, optimal cell dose, timing and frequency of cell injections, route of administration, or the use of combination therapy. This lack of consensus necessitates a comprehensive investigation to clarify these crucial yet undefined factors in cell-based therapy for CP patients. In this commentary, we discuss and compare the trends in Gross Motor Function Measure-66 following intrathecal injection of umbilical cord blood mononuclear cells (UCB-MNCs) and umbilical cord tissue mesenchymal stromal cells (UCTMSCs) in children with CP. Our study revealed that MNC injections led to earlier improvements in gross motor function, whereas MSC applications resulted in more sustainable changes. These findings provide key insights into the efficacy of different cell types, which will be beneficial for future studies and for refining cell-based therapy protocols for CP treatment.

Objective: Polycystic ovary syndrome (PCOS) is one of the most important causes of infertility, irregular menstrual cycles, and anovulation in women. The current study aimed to investigate the therapeutic effects of Althaea officinalis L. (A. officinale) extract on PCOS in rats.

Materials and methods: In this experimental study, 70 rats in 7 groups (n=10/group) were studied for three weeks as follows; healthy control (HC), patient (PCOS), metformin (PCOS+MET), A. officinale treatment (PCOS+250 and 500 mg/kg A. officinale) and synergistic (PCOS+MET+250 and 500 mg/kg A. officinale) groups. Luteinizing hormone (LH), folliclestimulating hormone (FSH), progesterone (P) and testosterone (T) levels as well as inflammatory cytokines were measured. Total antioxidant capacity and lipid peroxidation levels were analyzed in ovarian tissue. The expression of GLUT-4, AKT, PI3K, PTEN genes and Ki-67 was assessed by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively.

Results: A. officinale alone and especially in combination with MET moderated inflammatory and antioxidant parameters compared to the PCOS and MET groups. A. officinale in synergistic groups increased the apoptosis of granulosa cells by activating the PI3K/AKT pathway, resulting in a rise in the number of Ki-67 positive cells (P<0.05). Furthermore, following A. officinale treatment the LH/FSH rate decreased and FSH and P increased (P<0.05). Also, A. officinale extract could effectively normalize estrus cycle duration close to the normal group.

Conclusion: The extract of A. officinale, in combination with metformin, can enhance the hypothalamic-pituitaryovary (HPO) axis with synergistic anti-inflammatory and antioxidant effects. Additionally, the extract showed apoptotic effect on cystic granulosa cells.

Veno-occlusive disease with immunodeficiency (VODI) syndrome is a rare genetic disorder characterized by immune system irregularities and a significant mortality rate, despite its infrequency. SP110, situated on chromosome 2q37.1, plays a pivotal role in VODI syndrome, and its association with tuberculosis has been extensively studied. The identification of SP110 mutations holds promise for accelerating the diagnosis and treatment of VODI syndrome, by providing a comprehensive panel for diagnosis and potentially leading to targeted therapies. In this case study, we examined a three-year-old girl born to a consanguineous union who was suspected of having an immunodeficiency disorder. Whole-exome sequencing (WES) and clinical assessments were conducted to screen for and confirm potentially pathogenic mutations. The detected mutation was further analyzed using bioinformatics tools to forecast its impact on protein structure. WES analysis revealed a novel deletion-insertion mutation, c.1181-1182delAGinsT, within SP110. Protein analysis indicated substantial structural modifications in the SP110 protein. This study identified a novel deletion-insertion mutation as a potential contributor to VODI syndrome by affecting the functionality of the SP110 protein. By including various mutations associated with the SP110 gene, this study aimed to expedite diagnosis by creating a comprehensive panel for VODI syndrome.

Objective: CD22, as a surface protein of B cells, is used in the diagnosis and target-specific immunotherapy of B-cell malignancies. SpyTag and SpyCatcher, on the other hand, are two covalently coupled proteins capable of developing a bi- or multi-specific modular protein. The aim of this study was to develop FITC-conjugated SpyCatcher-SpyTagged anti-CD22 Nanobody (FITC-SpyC-SpyT-CD22Nb) to recognize CD22 on the surface of malignant B cells.

Materials and methods: In this experimental study, the SpyTag-CD22Nb construct was subcloned into a pET22 vector and expressed in E. coli BL21 (DE3). After purification using His-tag affinity chromatography, the size of the eluted protein was confirmed on a Western blot. In addition, the SpyCatcher protein, subcloned into pET28, was expressed in E. coli BL21 (DE3), purified by His-tag affinity chromatography and subjected to FITC labeling. FITC-SpyCatcher and SpyTag-CD22Nb were coupled in a 1:1 molar ratio. The specific binding of the produced FITC-SpyC-SpyT-CD22Nb was tested using CD22+ Raji and CD22- K562 cell lines and was evaluated by flow cytometry.

Results: SpyTag-CD22Nb and SpyCatcher were successfully expressed in E. coli BL21 (DE3). The 1:1 molar ratio of SpyTag-CD22Nb and FITC-SpyCatcher successfully formed FITC-SpyC-SpyT-CD22Nb at room temperature. The flow cytometry results showed that FITC-SpyC-SpyT-CD22Nb specifically binds to the CD22+ Raji cells, while there is no binding to the CD22- K562 control cells.

Conclusion: The novel FITC-SpyC-SpyT-CD22Nb produced in the present study is capable of detecting the surficial expression of CD22. According to our findings, FITC-SpyC-SpyT-CD22Nb is applicable for specific targeting of CD22 in a therapeutic manner, i.e., chimeric antigen receptor (CAR)-T cell therapy and antibody drug conjugates (ADCs).

Objective: The spliced form of X-box binding protein 1 (XBP1s) is a key transcription factor in the unfolded protein response (UPR), an adaptive mechanism for cell survival. Many studies demonstrated the induced expression of XBP1s in various cancers, including hepatocellular carcinoma (HCC). Such upregulated expression is linked to an enhancement of cell proliferation, migration, and improvement of the survival rate. In this study, we aimed to assess the therapeutic potential of targeting XBP1s, by specific decoy oligodeoxynucleotide (ODN) and evaluated the cancerous phenotypes in Huh-7 cells.

Materials and methods: In this experimental study, we transfected Huh-7 cells with XBP1s decoy oligonucleotide (ODN). Subsequently, we assess some cellular features, including viability, migration capacity, proliferation potential, and apoptosis. Therefore, various techniques included wound healing test, BrdU, and annexin/PI assays. Additionally, the colony formation capacity was evaluated. The mRNA expression levels of BAX, BCL-2, c-MYC, CCND1, MMP-9, CDH1, and CD133 were quantified by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results: Transfection of Huh-7 cells by XBP1s decoy ODN led to significant down-regulation of c-Myc, CCND1, MMP-9, BCL-2 and CD133 and up-regulation of CDH1 and BAX transcriptional expressions in comparison with the vehicle group. Our results also demonstrated that transfection of XBP1s-decoy reduced HCC cell viability, proliferation, migration capacity as well as colonization ability in comparison with the vehicle group.

Conclusion: These findings proposed the potential application of XBP1s-decoy ODN to reduce cancerous phenotypes such as cell proliferation, cell migration and apoptosis induction in the Huh-7 cell line. More experiments on other cell lines and primary cells could validate our results.

Objective: Breast cancer is a prevalent and heterogeneous disease, with human epidermal growth factor receptor-2 (HER2) overexpression occurring in over 20% of cases. Poncirin, a biologically active flavonone derived from the immature dried fruits of Poncirus trifoliata, is a 7-O-neohesperidoside of isosakuranetin with a well-documented history in traditional Chinese medicine for its health-promoting properties. While the previous research hinted at its potential as an anticancer agent, its specific effects on HER2 overexpressing breast cancer cells remain largely unexplored. The aim of this study is to investigate the specific effects of Poncirin, on HER2 overexpressing breast cancer cells.

Materials and methods: In experimental study, we assessed cell proliferation using the CCK-8 assay and explored cell migration and invasion with transwell assays. Additionally, we evaluated colony formation ability and examined apoptosis through the acridine orange/ethidium bromide (AO/EB) and Annexin V-fluorescein isothiocyanate (FITC)/ propidium iodide (PI) staining methods. The study also delved into the molecular mechanisms involved by scrutinizing the phosphatidylinositol 3-kinase/serine-threonine protein kinase (PI3K/AKT) signaling pathway via Western blotting. Furthermore, the researchers conducted in vivo experiments using mouse models to corroborate the findings in a living organism.

Results: Poncirin demonstrated a remarkable ability to selectively inhibit proliferation and metastasis of HER2 overexpressing breast cancer cells. Mechanistically, the compound seemed to exert its effects by modulating the PI3K/AKT signaling pathway, implying its central role in the observed anticancer effects. These findings were further substantiated by in vivo experiments, which consistently showed a reduction in tumor growth when poncirin was administered.

Conclusion: This study underscores potential of poncirin as a potent agent for restraining the growth and metastasis of HER2 overexpressing breast cancer cells. The evidence suggests that poncirin efficacy may be attributed to its modulation possibly through PI3K/AKT pathway.