Long noncoding RNA TP53TG1 (lncRNA TP53TG1) is involved in regulating the proliferation, migration, invasion, and apoptosis of various cancer cells, but there are few reports on its role in other cells.

To investigate the effects and pathways of lncRNA TP53TG1 on the proliferation and differentiation of human stem cells from the apical papilla.

Human stem cells from the apical papilla were isolated and cultured, and then transfected with lncRNA TP53TG1 overexpression lentivirus. RT-qPCR was used to detect the overexpression efficiency of lncRNA TP53TG1. Western blot assay was used to detect the relative expression levels of PI3K, AKT, ERK, P38, Smad3, and their phosphorylated proteins. Human stem cells from the apical papilla were divided into the empty lentiviral vector transfection group and the lncRNA TP53TG1 overexpression group. CCK-8 assay was used to measure the cell proliferation. Alkaline phosphatase activity was detected by alkaline phosphatase staining on day 5 of osteogenic induction. Formation of mineralized nodules was detected by alizarin red staining on day 21 of osteogenic induction. RT-qPCR was used to detect the mRNA expression levels of dentin sialophosphoprotein, Runt-related transcription factor 2, dentin matrix protein 1, and bone sialoprotein on days 3, 7, and 14 of osteogenic induction. Western blot assay was used to detect the protein expression levels of dentin sialophosphoprotein and Runt-related transcription factor 2 on days 3, 7, and 14 of osteogenic induction.

(1) RT-qPCR results showed that the lentivirus was successfully integrated into the genome of stem cells from the apical papilla. Western blot assay results showed that overexpression of lncRNA TP53TG1 up-regulated the protein levels of p-PI3K and p-AKT without affecting the expression of phosphorylated proteins in other pathways. (2) Starting from day 3 of cell culture, overexpression of lncRNA TP53TG1 significantly promoted the proliferation of stem cells from the apical papilla. (3) In the process of inducing odontogenic differentiation of stem cells from the apical papilla, overexpression of lncRNA TP53TG1 promoted the expression of odontogenic and osteogenic differentiation-related genes and proteins, significantly increased alkaline phosphatase activity and mineralized nodule formation. (4) The results show that lncRNA TP53TG1 may promote the odontogenic and osteogenic differentiation of stem cells from the apical papilla by activating the PI3K/AKT signaling pathway.

Numerous studies have indicated that pyroptosis plays a key role in the progression of cancer. In recent years, research has shown that pyroptosis is inextricably linked to the occurrence, development, and treatment of breast cancer. The development of effective pyroptosis-based therapeutic strategies has become a hot topic in the field of breast cancer treatment.

To comprehensively analyze the mechanisms of pyroptosis, explore the role of pyroptosis in the anti-tumor effects in breast cancer, and its potential application value in clinical treatment.

Using English search terms “pyroptosis, breast cancer, inflammasome, gasdermin, caspase, drug resistance, treatment”, PubMed database was searched for articles published from inception to August 2024. Through the preliminary screening of reading titles and abstracts, literature with poor relevance to the research content, outdated information, repeated views, and lack of authority was excluded. Finally, 121 articles were included for review.

Pyroptosis is a special form of programmed cell death that is carried out by the activation of the gasdermin family of proteins, showing potential application value in the treatment of breast cancer. Long-term or improper treatment can lead to drug resistance in cancer cells; research on the mechanism of pyroptosis helps to overcome resistance deficiencies. Pyroptosis can trigger immunogenic cell death, promoting the release of tumor-specific antigens, thereby activating the immune system and enhancing its ability to recognize and clear tumor cells. The expression levels of pyroptosis-related genes can serve as prognostic indicators for breast cancer, helping to assess patients’ treatment responses and survival periods. Research on the mechanisms of pyroptosis can provide new strategies for the treatment of breast cancer, such as targeted drugs and therapeutic methods that induce pyroptosis, contributing to the realization of personalized treatment plans for breast cancer.

Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome, but the specific mechanism is not yet clear.

To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.

A total of 70 SD rats were randomly divided into a normal control group (n=10), a model group (n=15), a western medicine group (n=15), a low-dose Huosui Formula group (n=15), and a high-dose Huosui Formula group (n=15). Except for the normal control group, the other four groups were injected with dimethylbenzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models. After modeling, the normal control group and the model group were given normal saline; the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg, and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula, respectively, by intragastric administration once a day for 28 consecutive days. Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation. Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.

(1) Compared with the normal control group, peripheral blood leukocyte, neutrophil, hemoglobin, platelet, and CD4⁺, CD4⁺/CD8⁺ levels were decreased in the model group significantly (P < 0.05), while CD4⁺PD-1⁺, CD8⁺PD-1⁺, CD4⁺CTLA-4⁺, and CD8⁺CTLA-4⁺ expressions were significantly upregulated (P < 0.05). (2) In all dosage groups, myelopoietic proliferation was increased compared with the model group, with no significant difference between the groups (P > 0.05). (3) Compared with the model group, leukocytes, hemoglobin, platelets, and CD4⁺, CD4⁺/CD8⁺ were significantly elevated in the high-dose Huosui Formula group (P < 0.05), the expression of CD8⁺ was significantly lower (P < 0.05), and the levels of CD4⁺PD-1⁺, CD8⁺PD-1⁺, CD4⁺CTLA-4⁺, and CD8⁺CTLA-4⁺ were down-regulated but not statistically significant (P > 0.05). (4) The western medicine group and the high-dose Huosui Formula group showed similar efficacy. The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group. These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats, increase the levels of CD4⁺, and CD4⁺/CD8⁺ while down-regulate the expression levels of CD4⁺PD-1⁺, CD8⁺PD-1⁺, CD4⁺CTLA-4⁺, and CD8⁺CTLA-4⁺. These observations suggest a link to the negative immunoregulation mechanism.

Human pluripotent stem cell-derived cardiomyocytes offer an ideal cellular resource for studying heart diseases, conducting drug screening, developing in vitro heart models, and exploring potential cell therapies. However, human pluripotent stem cell-derived cardiomyocytes are characterized by immaturity with limited specific gene expression, low Ca²⁺ processing levels, and underdeveloped structural, metabolic, and electrophysiological features. These limitations significantly impede the application of human pluripotent stem cell-derived cardiomyocytes.

To review the academic progress and clinical application of promoting the maturation of human pluripotent stem cell-derived cardiomyocytes by in vitro synthetic microenvironment.

CNKI, WanFang, VIP, PubMed, Web of Science, and Medline databases were searched, with “human pluripotent stem cells, human myocardial cells, hPSC-CMs, mature, OA, human pluripotent stem cell-derived cardiomyocytes, hPSC-CMs” as English search terms and “human pluripotent stem cells, cardiomyocytes, mature, OA, hPSC-CMs” as Chinese search terms. All relevant literature published from January 2002 to July 2024 was retrieved and 82 articles were included in the review.

(1) In recent years, in vitro synthetic microenvironments have attracted extensive attention due to their excellent intrinsic properties such as stiffness, plasticity, nanoscale morphology, and chemical functionality. (2) Human pluripotent stem cell-derived cardiomyocytes can be used as an effective platform for the treatment of cardiovascular diseases. (3) Mechanical stimulation, electrical stimulation, addition of biochemical molecules, and three-dimensional culture methods are effective methods to promote the maturation of human pluripotent stem cell-derived cardiomyocytes, which can further promote the clinical application of human pluripotent stem cell-derived cardiomyocytes.

Bone marrow mesenchymal stem cells are the main effector cells for bone formation. With the increase of age, the regenerative ability of bone marrow mesenchymal stem cells is weakened and the differentiation function is impaired, leading to poor osteoporosis. Therefore, restoring the regenerative capacity and cellular function of aged bone marrow mesenchymal stem cells is essential for the effective treatment of osteoporosis.

To investigate the effects of passage 3 and passage 11 bone marrow mesenchymal stem cells-derived exosomes of young rats on the aging of bone marrow mesenchymal stem cells derived from elderly rats.

Bone marrow mesenchymal stem cells from 6-8-week-old female SD rats were isolated and cultured, and passaged to the passages 3 and 11, respectively. Then, exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were extracted. Bone marrow mesenchymal stem cells from 18-month-old female SD rats were isolated and cultured, passaged to passage 3, and divided into 3 groups. The control group was routinely cultured, and the other two groups were intervened with exosomes from passages 3 and 11 bone marrow mesenchymal stem cells. After 48 hours of exosome intervention, the expression of β-galactosidase in the nucleus was detected by β-galactosidase staining kit. The expression of aging-related genes was detected by qRT-PCR. The expression differences of miRNA in exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were compared by Small RNA sequencing.

(1) Compared with the control group and passage 11 bone marrow mesenchymal stem cell-derived exosomes group, the β-galactosidase activity of bone marrow mesenchymal stem cells of aged rats was significantly lower in the passage 3 bone marrow mesenchymal stem cell-derived exosomes group. (2) Compared with the control group, the expression of aging-related genes p21 and p16 was significantly reduced in the passage 3 bone marrow mesenchymal stem cell-derived exosome group (P < 0.05), while there was no significant difference in the expression of aging-related genes p21 and p16 in the passage 11 bone marrow mesenchymal stem cell-derived exosome group. (3) Sequencing results showed that there was a significant difference in the expression of miRNAs in the two exosomes, among which the miRNAs with the most significant expression differences were let-7c-5p, let-7b-5p, miR-320-3p, and miR-26a-5p. KEGG analysis results showed that significantly different miRNA enrichment pathways include mTOR, AMPK and other aging-related signaling pathways. The above results indicate that passage 3 bone marrow mesenchymal stem cell-derived exosomes have the ability to reverse the aging of bone marrow mesenchymal stem cells in aged rats.

Extracellular vesicles have received extensive attention in the field of bone defect regeneration and repair in recent years. However, natural extracellular vesicles have deficiencies in sustained controlled release, tissue targeting, and drug loading capacity. Therefore, the introduction of engineering strategies to modify extracellular vesicles to enhance their therapeutic efficacy has become a research hotspot.

To review the role and application progress of engineered extracellular vesicles in the regeneration and repair of bone defects.

PubMed, Web of Science, CNKI, and WanFang databases were searched for relevant articles published in the past fifteen years. The search terms were “engineering, extracellular vesicles, exosomes, bone defect, bone regeneration, bone repair” in Chinese and English. After removal of poorly related, outdated, and duplicate studies by screening, 93 articles were finally included for review according to inclusion criteria.

(1) Extracellular vesicles are primarily isolated based on their density, size, immunoaffinity, and surface charge. After isolation, extracellular vesicles are characterized using imaging techniques, size- and counting-based techniques, and flow cytometry. (2) Extracellular vesicles stimulate bone regeneration by regulating immunity, angiogenesis, and proliferation and differentiation of target cells. (3) The engineering strategies of extracellular vesicles include surface modification and cargo loading. (4) The introduction of bone morphogenetic protein 2, mutant hypoxia-inducible factor-1α, vascular endothelial growth factor, miRNA and other bioactive factors into extracellular vesicles through engineering strategies can enhance their regenerative repair ability for bone defects.

Accurate early diagnosis and timely reperfusion therapy are important prerequisites for saving the lives and improving the prognosis of patients with acute myocardial infarction. Therefore, it is important to find ideal biomarkers for early diagnosis of acute myocardial infarction.

To analyze key genes associated with neutrophils by acute myocardial infarction through bioinformatics and machine learning to explore new biomarkers.

Differentially expressed genes were identified based on the Gene Expression Omnibus (GEO) database and Limma R package. Deconvolution algorithm was used to explore the immune cells infiltration level. Then, acute myocardial infarction and neutrophils-related biomarkers were screened by weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks, machine learning, and functional enrichment analysis. Receiver operating characteristic curve analysis was conducted to assess the diagnostic efficacy of biomarkers for acute myocardial infarction. Targeted drugs for biomarkers were screened through the STITCH and Herb database. Finally, the hospitalized patients who were first diagnosed with acute myocardial infarction in the Department of Cardiology of Affiliated Hospital of Guizhou Medical University from March to June 2023 were used as the experimental group, and the hospitalized patients who had no ischemic changes on electrocardiograms and no stenosis on coronary angiograms during the same period were used as the control group. Peripheral blood of the patients in the two groups was collected. The relative expressions of the genes were verified in the human peripheral blood samples by RT-qPCR.

(1) A total of 2 349 differentially expressed genes were obtained, and immune infiltration analysis revealed differences in immune cell scores such as B cells memory, NK cells resting, and Neutrophils between the disease and normal groups. (2) Using WGCNA, two gene modules, ME green and ME turquoise, were found to exhibit the highest correlation with neutrophil fine with acute myocardial infarction. (3) Twenty-four differential module genes were obtained after intersecting with differentially expressed genes. Functional enrichment analysis revealed that they were associated with a variety of processes such as innate immune response and defense response to bacteria. KEGG results showed that they were mainly associated with the tumor necrosis factor signaling pathway. (4) The genes mined by the machine learning algorithm took the intersection to obtain three genes, namely, S100A12, PTCH1, and LOC400499, all of which were greater than 0.7 by the area under the receiver operating characteristic curve in both the GSE48060 and GSE66360 datasets. They were considered as potential biomarkers. (5) Based on the STITCH and Herb databases, 11 target drugs were found for S100A12 and a total of 6 target drugs were found for PTCH1. (6) RT-qPCR results showed that S100A12, PTCH1, and LOC400499 were significantly differentially expressed in acute myocardial infarction patients compared with controls (P < 0.05). (7) S100A12, PTCH1, and LOC400499 may be potential diagnostic biomarkers for acute myocardial infarction, but their specificity in relation to acute myocardial infarction needs to be further investigated, in which S100A12 may be a potential target for regulating acute myocardial infarction.

Autologous or artificial bone grafts have been widely used to repair maxillofacial bone defects clinically, but these methods still suffer from insufficient osteogenesis. Bone marrow mesenchymal stem cells play a key role in the bone formation. Notably, ectoderm-derived jaw bone marrow mesenchymal stem cells have stronger proliferation and osteogenic differentiation capacity compared with mesoderm-derived iliac bone marrow mesenchymal stem cells, elucidating the key mechanisms involved. It is expected to provide a new strategy for the repair of craniomaxillofacial bone defects.

To compare the biological differences between human jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells and identify the key regulatory genes.

(1) Jaw bone and iliac bone were collected from three patients with alveolar cleft. Primary bone marrow mesenchymal stem cells were isolated and cultured. Cell proliferation ability was detected by colony formation assay. Cell senescence was detected by β-galactosidase staining assay. Senescence and osteogenesis-related protein expression levels were detected by western blot assay. Osteogenic ability was detected by alizarin red staining after osteogenic induction solution treatment. (2) Jaw bone marrow mesenchymal stem cells and iliac bone marrow mesenchymal stem cells were subjected to transcriptome and differential gene expression analysis to find the 20 genes with the largest differential expression and identify the key regulatory factors. (3) The gene in iliac bone marrow mesenchymal stem cells were knocked down to comparatively analyze the changes in self-renewal, anti-aging and osteogenic capacity of iliac bone marrow mesenchymal stem cells. (4) The gene-edited iliac bone marrow mesenchymal stem cells were loaded into β-tricalcium phosphate scaffolds and implant into nude mice for 8 weeks. The scaffolds were stained with Masson staining and immunofluorescence staining to observe the difference in osteogenic capacity.

(1) Jaw bone marrow mesenchymal stem cells have stronger proliferation, anti-aging and osteogenic differentiation abilities compared to iliac bone marrow mesenchymal stem cells. (2) By transcriptome analysis, we identified HOXA10 as a highly up-regulated core transcription factor in iliac bone marrow mesenchymal stem cells. (3) After knocking down HOXA10 in iliac bone marrow mesenchymal stem cells, we observed a significant increase in proliferation, anti-aging, and osteogenic differentiation abilities. (4) After HOXA10 knocked-down iliac bone marrow mesenchymal stem cells/β-tricalcium phosphate was implanted subcutaneously on the back of nude mice, and their bone formation ability was stronger. (5) The above results suggest that HOXA10 is a key regulatory gene that determines the proliferative, anti-aging and osteogenic differentiation abilities of bone marrow mesenchymal stem cells. HOXA10 gene-modified iliac bone marrow mesenchymal stem cell transplantation can be used as a potential application strategy for repairing maxillofacial bone defects.

Enhancing the differentiation of induced pluripotent stem cells into lung stem cells is crucial for repairing lung injuries. NKX2.1 is the earliest marker of lung epithelial differentiation and plays a significant regulatory role in lung development. However, the impact of its expression on the differentiation of induced pluripotent stem cells into lung stem cells remains inadequately understood.

To investigate the effect of NKX2.1 on the differentiation of induced pluripotent stem cells into lung stem cells.

Induced pluripotent stem cells were cultured in vitro. The expression of specific pluripotent stem cell genes was assessed using real-time fluorescence quantitative PCR. NKX2.1 was overexpressed in induced pluripotent stem cells, which were then induced to differentiate into lung stem cells. The expression of FoxA2, SOX9, and P63 was determined via quantitative PCR and immunofluorescence on day 7 of induction of differentiation. The expression of the alveolar marker SPB and SPC was evaluated through immunofluorescence staining on day 7 of induction of differentiation.

(1) Induced pluripotent stem cells in vitro were tightly packed and showed typical clonoid growth and significantly expressed stem cell-specific genes OCT-4, SOX2, and NANOG. (2) Compared with the non-transfected control group, the expression of NKX2.1 in human induced pluripotent stem cells was significantly increased in the NKX2.1 overexpression group (P < 0.000 1). (3) Seven days after induction of differentiation, compared with the non-transfected control group, the expression of lung stem cell-related markers FoxA2, SOX9, and P63 was significantly increased in the NKX2.1 overexpression group (P < 0.000 1). (4) Thirteen days after induction of differentiation, compared with the non-transfected control group, the fluorescence intensity of alveolar cell marker molecules SPB and SPC increased significantly in the overexpression NKX2.1 group. The results show that NKX2.1 can promote the differentiation of induced pluripotent stem cells into lung stem cells.

Premature ovarian failure has manifested a trend of younger, and stem cell therapy has been progressively implemented in clinical practice in recent years. Nevertheless, given the extensive range of sources and variegated existence of stem cells in diverse tissues, certain disparities prevail in their biological characteristics and functions. In this paper, the therapeutic efficacies of dissimilar sources of mesenchymal stem cells on animal models of premature ovarian failure were contrasted, with the aim of providing a basis for the clinical application of stem cells.

The animal model experiments of mesenchymal stem cell therapy for premature ovarian failure were retrieved from PubMed, The Cochrane Library, and EMbase, as well as Chinese databases such as CNKI, WanFang, VIP, and China Biomedical Literature Service. The search period extended from the inception to December 31, 2023. Two researchers independently screened the literature, extracted and analyzed the data. The quality of the included studies was evaluated by means of the SYRCLE animal experiment bias risk assessment table. Main outcome measures: Follicle stimulating hormone, estradiol, luteinizing hormone, the quantity of follicles at all levels. Secondary outcome measure: Pregnancy rate. Network meta-analysis, mapping, and tabulation were executed using Stata 17.0 software after assessing the risk of bias in the included studies.

Totally 24 animal experiment studies were incorporated, and the overall quality of the literature was mediocre, encompassing 7 distinct sources of mesenchymal stem cells. They were umbilical cord-derived mesenchymal stem cells, menstrual blood-derived mesenchymal stem cells, placenta-derived mesenchymal stem cells, human cord blood-derived mesenchymal stem cells, bone marrow-derived mesenchymal stem cells, adipose-derived mesenchymal stem cells, and amnio-derived mesenchymal stem cells. The network meta-analysis demonstrated that (1) in contrast to the blank group, mesenchymal stem cells from various sources were effective in enhancing the pregnancy rate and estradiol, reducing follicle-stimulating hormone and luteinizing hormone, augmenting the number of follicles at all levels, and diminishing the number of atretic follicles. (2) According to the area map under the cumulative sequencing curve, the three stem cells with the most prominent efficacy in improving estradiol levels were umbilical cord-derived mesenchymal stem cells (72.7%) > adipose-derived mesenchymal stem cells (72.6%) > menstrual blood-derived mesenchymal stem cells (71.7%). (3) The three kinds of stem cells with the highest efficacy in reducing follicle-stimulating hormone levels were the adipose-derived mesenchymal stem cells (96.3%) > human cord blood-derived mesenchymal stem cells (65.4%) > umbilical cord-derived mesenchymal stem cells (63.9%). (4) The three kinds of stem cells with the highest efficacy in reducing luteinizing hormone levels were adipose-derived mesenchymal stem cells (100.0%) > umbilical cord-derived mesenchymal stem cells (51.6%) > human cord blood-derived mesenchymal stem cells (46.8%). (5) The top three kinds of stem cells for increasing the number of primordial follicles were human cord blood-derived mesenchymal stem cells (76.3%) > umbilical cord-derived mesenchymal stem cells (75.5%) > menstrual blood-derived mesenchymal stem cells (57.5%). (6) The top three kinds of stem cells for increasing the number of primary follicles were umbilical cord-derived mesenchymal stem cells (75.3%) > adipose-derived mesenchymal stem cells (53.0%) > the placenta-derived mesenchymal stem cells (51.7%). (7) The top three kinds of stem cells for increasing the number of secondary follicles were adipose-derived mesenchymal stem cells (76.1%) > menstrual blood-derived mesenchymal stem cells (66.8%) > umbilical cord-derived mesenchymal stem cells (66.5%). (8) The top three kinds of stem cells in reducing the number of atretic follicles were adipose-derived mesenchymal stem cells (99.9%) > bone marrow-derived mesenchymal stem cells (68.1%) > umbilical cord-derived mesenchymal stem cells (53.4%).

(1) For animal models of premature ovarian failure, the results of the network meta-analysis disclosed that various stem cell transplantation treatments were preponderant over the blank or placebo group to varying extents, and the efficacies were comparable. (2) The results indicated that umbilical cord-derived mesenchymal stem cells were the most frequently utilized and adipose-derived mesenchymal stem cells were the most potent. More high-quality experimental study data are requisite in the future for further validation.