Pengzhen Wang

As follow, Figure 4A Error The original version of this article has been updated.

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease characterized by left ventricular hypertrophy and excessive myocardial contraction. E

Objective: Potassium voltage-gated channel sub-family A member 1 (Kv1.1), as a shaker homolog potassium channel, displays a special mechanism for posttranscriptional regulation called RNA editing. Adenosine deaminase acting on RNA 2 (ADAR2) can cause abnormal editing or loss of normal editing, which results in cell damage and related diseases. The relationship between Kv1.1 and editing enzyme ADAR2 in epileptic rats remains incompletely understood. We aimed to investigate the neuroprotective role of ADAR2 and its relationship with Kv1.1 in epileptic rats and the SH-SY5Y neuroblastoma cell line. Material and Methods: A rat epilepsy model was induced in vivo using lithium chloride–pilocarpine. We investigated the effect of ADAR2 on epileptic rats through Western blotting, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and histological analysis. Western blotting was aimed at investigating the effect of overexpression of ADAR2 and Kv1.1-interfering RNA (si-Kv1.1) for neuronal apoptosis. Results: The overexpression of ADAR2 in epileptic rats led to the increased mRNA and protein expression of Kv1.1 (P < 0.001) and B-cell leukemia/lymphoma 2 protein (Bcl-2) (P < 0.001), whereas the decreased expressions of Bcl-2-associated X protein and cleaved caspases-3/7 at protein levels (P < 0.0001; P < 0.0001; P < 0.01) detected by Western blotting and qRT-PCR experiments. Hematoxylin and eosin staining and Nissl staining revealed the neuroprotection provided by ADAR2 overexpression. The experiments demonstrated that Kv1.1 was regulated by ADAR2. ADAR2 overexpression increased neuronal survival in in vivo experiments through the elevation of Bcl-2 levels (P < 0.05) and reduction of cleaved caspase-3/7 activity (P < 0.0001; P < 0.01). In the recovery experimental group that involved silencing Kv1.1, the beneficial effects of overexpressing ADAR2 were no longer observed (P < 0.05). Conclusion: Our findings confirm that the upregulation of ADAR2 promotes Kv1.1 protein expression, which ultimately reduces neuronal damage in the hippocampus of animals with epilepsy.

A three‐dimensional alginate‐coated scaffold (GAIS) was constructed in the present study to showcase the multidifferentiation potential of peripheral blood mesenchymal stem cells (PBMSCs) and to investigate the role and mechanism by which Icariin (ICA)/stromal cell‐derived factor (SDF‐1α)/PBMSCs promote damaged articular repair. In addition, the ability of ICA, in combination with SDF‐1α, to promote the migration and proliferation of stem cells was validated through the utilization of CCK‐8 and migration experiments. The combination of ICA and SDF‐1α inhibited the differentiation of PBMSCs into cartilage, as demonstrated by in vivo experiments and histological staining. Both PCR and western blot experiments showed that GAIS could upregulate the expression of particular genes in chondrocytes. In comparison to scaffolds devoid of alginate (G0), PBMSCs seeded into GAIS scaffolds exhibited a greater rate of proliferation, and the conditioned medium derived from scaffolds containing SDF‐1α enhanced the capacity for cell migration. Moreover, after a 12‐week treatment period, GAIS, when successfully transplanted into osteochondral defects of mice, was found to promote cartilage regeneration and repair. The findings, therefore, demonstrate that GAIS enhanced the in vitro capabilities of PBMSCs, including proliferation, migration, homing and chondrogenic differentiation. In addition, ICA and SDF‐1α effectively collaborated to support cartilage formation in vivo. Thus, the ICA/SDF‐1α/PBMSC‐loaded biodegradable alginate‐gelatin scaffolds showcase considerable potential for use in cartilage repair.

Icariin (ICA) is a typical flavonoid glycoside derived from epimedium plants. It has both anabolic and anti-catabolic effects to improve bone mineral density and reduce bone microstructural degradation. However, the effect and underlying mechanism of ICA on the proliferation and metabolism of chondrocyte and synthesis of extracellular matrix are still unclear. This study aimed to investigate the role and regulation of far upstream element binding protein 1 (FUBP1) in chondrocytes treated with ICA to maintain homeostasis and suppress inflammatory responses. In the study, the effect of ICA on chondrocytes with overexpressed or silenced FUBP1 was detected by the MTS and single-cell cloning methods. The expression of hypoxia-inducible factor-1/2α (HIF-1/2α), FUBP1, matrix metalloproteinase (MMP)9, SRY-box transcription factor 9 (SOX9), and type II collagen (Col2α) in ATDC5 cells, a mouse chondrogenic cell line, treated with ICA was evaluated by immunoblotting. Western blotting revealed 1 µM ICA to have the most significant effect on chondrocytes. Alcian blue staining and colony formation assays showed that the promoting effect of ICA was insignificant in FUBP1-knockdown cells (P > 0.05) but significantly enhanced in FUBP1-overexpressed cells (P < 0.05). Western blot results from FUBP1-knockdown cells treated with or without ICA showed no significant difference in the expression of FUBP1, HIF-1/2α, MMP9, SOX9, and Col2α proteins, whereas the same proteins showed increased expression in FUBP1-overexpressed chondrocytes; moreover, HIF-2α and MMP9 expression was significantly inhibited in FUBP1-knockdown chondrocytes (P < 0.05). In conclusion, as a bioactive monomer of traditional Chinese medicine, ICA is beneficial to chondrocytes.

Stem cell therapy has been extensively studied to improve heart function following myocardial infarction; however, its therapeutic potency is limited by low rates of engraftment, survival, and differentiation. Here, we aimed to determine the roles of the β-catenin/Oct4 signaling axis in the regulation of long-term survival and angiogenesis of peripheral blood mesenchymal stem cells (PBMSCs). These cells were obtained from rat abdominal aortic blood. We showed that β-catenin promotes the self-renewal, antiapoptotic effects, and long-term survival of PBMSCs by activating the Oct4 pathway through upregulation of the expression of the antiapoptotic factors Bcl2 and survivin and the proangiogenic cytokine bFGF and suppression of the levels of the proapoptotic factors Bax and cleaved caspase-3. β-Catenin overexpression increased Oct4 expression. β-Catenin knockdown suppressed Oct4 expression in PBMSCs. However, β-catenin levels were not affected by Oct4 overexpression or knockdown. Chromatin immunoprecipitation assays proved that β-catenin directly regulates Oct4 transcription in PBMSCs. In vivo, PBMSCs overexpressing β-catenin showed high survival in infarcted hearts and resulted in better myocardial repair. Further functional analysis identified Oct4 as the direct upstream regulator of Ang1, bFGF, HGF, VEGF, Bcl2, and survivin, which cooperatively drive antiapoptosis and angiogenesis of engrafted PBMSCs. These findings revealed the regulation of β-catenin in PBMSCs by the Oct4-mediated antiapoptotic/proangiogenic signaling axis and provide a breakthrough point for improving the long-term survival and therapeutic effects of PBMSCs.

This study aimed to address the dilemma of low peripheral blood-derived mesenchymal stromal cell (PBMSC) activity and reduced phenotype in bone or cartilage tissue engineering. Rat PBMSCs (rPBMSCs) were obtained by density gradient centrifugation, and stromal cell characteristics were confirmed by flow cytometry (FCM) and multi-differentiation potential induction experiments. Cell growth curve, viability experiments, and clone formation experiments were performed by [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) and cell counting, and the cell cycle was confirmed by cell FCM. The proliferation signal pathway and stemness-related proteins were detected by molecular methods including Western blot and real-time polymerase chain reaction. CD73, CD90, and CD105 were highly expressed, and CD14, CD19, CD34, CD45, and HLA-DR were barely expressed in rPBMSCs. rPBMSCs possessed the potential to differentiate into chondrocytes, adipocytes, and osteoblasts under their respective induction conditions. Cell growth curve and viability experiments were performed under hypoxic conditions: 19% O₂, 5% O₂, and 1% O₂. Specifically, 5% O₂ accelerated the proliferation and expression of the stemness of PBMSCs. Cycle experiments proved that hypoxia promoted the cell transition from the G1 phase to the S phase. Molecular experiments confirmed that 5% O₂ hypoxia significantly elevated the expressions of hypoxia-inducible factor 1α and β-catenin and simultaneously the expressions of cycle-related genes including CyclinE/CDK2 and stemness-related genes including Nanog and SOX2. The appropriate concentration of hypoxia (i.e., 5% O₂) enhanced the proliferation and stemness of rPBMSCs and increased the multidirectional differentiation potential of stromal cells. The proposed culture method could improve the viability and maintain the phenotype of rPBMSCs in cartilage or bone tissue engineering.

Review Article Treatment and application of stem cells from different sources for cartilage injury: a literature review Pengzhen Wang, Shaoheng Zhang, Qingqi Meng, Pingping Zhu, Wei Yuan

Ovarian cancer is the seventh most common cancer and the second most common cause of cancer‑associated mortality among gynecological malignancies worldwide. The combination of antimitotic agents, such as taxanes, and the DNA‑damaging agents, such as platinum compounds, is the standard treatment for ovarian cancer. However, due to chemoresistance, development of novel therapeutic strategies for the treatment of ovarian cancer remains critical. Amentoflavone (AMF) is a biflavonoid derived from the extracts of Selaginella tamariscina, which has been used as a Chinese herb for thousands of years. A previous study demonstrated that AMF inhibits angiogenesis of endothelial cells and induces apoptosis in hypertrophic scar fibroblasts. In order to check the influence of AMF on cell proliferation, the effects of AMF on cell cycle and DNA damage were measured by cell viability, flow cytometry, immunofluorescence and western blotting assays in SKOV3 cells, an ovarian cell line. In the present study, treatment with AMF inhibited ovarian cell proliferation, increased P21 expression, decreased CDK1/2 expression, interrupted the balance of microtubule dynamics and arrested cells at the G2 phase. Furthermore, treatment with AMF increased the expression levels of phospho‑Histone H2AX (γ‑H2AX; a variant of histone 2A, that belongs to the histone 2A family member X) and the DNA repair protein RAD51 homolog 1 (Rad51), indicating the occurrence of DNA damage since γ‑H2AX and Rad51 are both key markers of DNA damage. Consistent with previous findings, the results of the present study suggest that AMF is a potential therapeutic agent for the treatment of ovarian cancer. In addition, the effects of AMF on cell cycle arrest and DNA damage induction may be the molecular mechanisms by which AMF might exert its potential therapeutic benefits in ovarian cancer.