Aiguo Li

Enocyanin (ENO), an anthocyanin extracted from grapes, has been shown to exert inhibitory effects on acid phosphatase and inflammation; however, its role in osteogenesis and bone formation is currently unknown. The present study aimed to investigate the effects of ENO on osteogenesis in vitro and bone formation in vivo, and to explore the rudimentary mechanisms. KusaO cells were employed to evaluate the osteogenic role of ENO in vitro by Alizarin red S staining, ALP staining, quantitative PCR and western blotting, and an in vivo analysis of the therapeutic effects of ENO on a femoral fracture model was performed using stereo microscope, micro‑CT and histological staining. To further investigate the underlying mechanisms, mRNA sequencing was employed to investigate the changes in gene expression and the downstream pathways after ENO treatment. The results showed that ENO could promote the osteogenic differentiation of KusaO cells in vitro and bone fracture regeneration in vivo. Mechanistically, ENO was highly related to bone formation, including the ‘Wnt signalling pathway’, ‘bone development’ and ‘bone mineralization’. In addition, matrix metalloproteinase 9 (MMP9) was identified as one of the targets of ENO in its promotional role in osteogenesis. In conclusion, ENO may represent a therapeutic candidate for bone regeneration in bone fractures by regulating osteogenesis and bone formation via MMP9.

The structure and composition of articular cartilage is complex, and its self-healing ability is limited, and thus, it is difficult to achieve ideal healing once the articular cartilage is damaged. Recently, three-dimensional (3D) printing technology has provided a new possibility for the repair of articular cartilage. Engineered cartilage tissues can be fabricated by superimposing customized inks, considering different geometric structures and components of tissues. 3D printing can be effectively used to manufacture high-precision structures with complex geometry, solving the shortcomings of traditional scaffold fabrication techniques. Gelatin methacrylate (GelMA) is modified gelatin and is currently a widely used 3D printing ink due to its photocrosslinking properties. With good biocompatibility and tunable physical properties, it can provide a good scaffold platform for cell proliferation and growth factor release. Given that the role of 3D printing technology in cartilage repair has been widely reported, this article reviews the research progress of 3D-printed GelMA-based biomaterials in articular cartilage tissue engineering. We focus primarily on how 3D printing technology addresses the existing challenges inherent to the field of articular cartilage tissue engineering. We accentuate the modifications implemented in GelMA-based 3D printing scaffolds to optimize articular cartilage regeneration. Additionally, we provide a comprehensive summary of the utilization of GelMA-based biomaterials incorporating various cells, growth factors, or other tissue components and highlight how these adaptations, in conjunction with the benefits of 3D printing technology, facilitate improvements the articular cartilage repair.

The occurrence and development of many diseases are highly associated with the aging of the body. Among them, osteoporosis (OP) is a common age-related disease that tends to occur in the elderly population and is highly related to the aging factors in the body. In the process of aging transmission, the senescence-related secretory phenotype (SASP) can convey the information about aging through the paracrine pathway and endocrine mechanism through the extracellular vesicles (EVs) connected to SASP. EVs can be used as a way of conduction to join the connection between micro-environmental aging and age-related illnesses. EVs are double-layer membranous vesicles separated or secreted from the cell membrane, which mainly include microvesicles (MVs) and exosomes. Vesicular bodies secreted by this exocrine form carry a variety of cell-derived related substances (including a variety of proteins, lipids, DNA, mRNA, miRNAs, etc). These substances are mainly concentrated in human body fluids, especially can be transported to all parts of the body with the blood circulation system, and participate in the interactions between cells. Osteoporosis is closely associated with aging and aging cells, suggesting EVs were active in this pathological process. In this article, the basic mechanisms of aging cells in the occurrence and progression of osteoporosis through EVs will be discussed, to explore the connection between aging and osteoporosis, thereby providing a new perspective on the occurrence and development as well as prevention and treatment of osteoporosis.

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.

Objective To investigate the clinical effect of large locking fusion plate and cable fixation in the treatment of Periprosthetic femoral fracture (PFF) after total hip arthroplasty (THA). Methods Clinical data of 15 cases of PFF after THA treated with large locking fusion plate and cable fixation from June 2012 to June 2019 in our hospital were retrospectively analyzed. These cases included 4 males and 11 females, whose age were 61-82 years old, with an average age of 71.3 years, 6 cases on the left side and 9 cases on the right side. We performed total hip arthroplasty in 10 patients and hemiarthroplasty in 5 patients. There were 5 cases of Type B1 fracture, 8 cases of type B2 fracture, and 2 cases of type B3 fracture. Preoperative and postoperative hip function, HSS score, Harris score and surgical complications were observed and evaluated. Results 15 patients were followed up 15-77 months after the operation (mean 36.9 months), and the hip function was significantly improved. The preoperative HSS score of knee function was 4.13±1.69, and the postoperative HSS score of knee function was 90.93±3.06, with11 excellent cases, 4 good cases and 0 general cases, with an excellent rate of 100%. Preoperative Harris score of knee function was 3.73±1.16. Harris score of hip function was 89.33±3.73 at the last follow-up. Among of all Harris scores, 10 cases were excellent, 3 cases were good, and 2 cases were general, with an excellent rate of 86.7%. Postoperative HHS and Harris scores were higher than those before surgery (P=0.031, PConclusion The application of large locking fusion plate and cable in the treatment of femoral periprosthetic fractures after total hip arthroplasty is simple, easy to operate, less complications, satisfactory clinical results, and worthy of promotion.

Amentoflavone is an active phenolic compound isolated fromSelaginella tamariscinaover 40 years. Amentoflavone has been extensively recorded as a molecule which displays multifunctional biological activities. Especially, amentoflavone involves in anti-cancer activity by mediating various signaling pathways such as extracellular signal-regulated kinase (ERK), nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and emerges anti-SARS-CoV-2 effect via binding towards the main protease (Mpro/3CLpro), spike protein receptor binding domain (RBD) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Therefore, amentoflavone is considered to be a promising therapeutic agent for clinical research. Considering the multifunction of amentoflavone, the current review comprehensively discuss the chemistry, the progress in its diverse biological activities, including anti-inflammatory, anti-oxidation, anti-microorganism, metabolism regulation, neuroprotection, radioprotection, musculoskeletal protection and antidepressant, specially the fascinating role against various types of cancers. In addition, the bioavailability and drug delivery of amentoflavone, the molecular mechanisms underlying the activities of amentoflavone, the molecular docking simulation of amentoflavone throughin silicoapproach and anti-SARS-CoV-2 effect of amentoflavone are discussed.

Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a multifunctional protein participated in diverse cellular processes, including chromosome remodeling, cell differentiation and development. CHD1L is a regulator of chromosomal integrity maintenance, DNA repair and transcriptional regulation through its bindings to DNA. By regulating kinds of complex networks, CHD1L has been identified as a potent anti-apoptotic and pro-proliferative factor. CHD1L is also an oncoprotein since its overexpression leads to dysregulation of related downstream targets in various cancers. The latest advances in the functional molecular basis of CHD1L in normal cells will be described in this review. As the same time, we will describe the current understanding of CHD1L in terms of structure, characteristics, function and the molecular mechanisms underlying CHD1L in tumorigenesis. We inference that the role of CHD1L which involve in multiple cellular processes and oncogenesis is well worth further studying in basic biology and clinical relevance.

Articular cartilage injury or defect is a common disease and is mainly characterized by cartilage degradation because of chondrocyte inflammation. By now, there are no effective drugs and methods to protect articular cartilage from degradation. Icariin (ICA) is a typical flavonoid compound extracted from Epimedii Folium with anti-inflammatory and bone-protective effects. Our previous studies demonstrate that ICA up-regulates HIF-1α expression and glycolysis in chondrocytes and maintains chondrocyte phenotype. As another member of HIFs family, HIF-2α always plays a key role in inflammation. The effect of ICA on HIF-2α is unclear by now. In this study, we not only confirmed the findings in our previous study that ICA promoted chondrocyte vitality and extracellular matrix (ECM) synthesis, but also the anti-inflammatory effect of ICA. In bone defect mice, ICA inhibited the expressions of NF-κB and HIF-2α. In TNF-α-treated ADTC5 chondrocytes, ICA neutralized the activation of IKK (IKK phosphorylation), the phosphorylation of IkB and NF-κB and the expression of HIF-2α. Furthermore, ICA inhibited the nucleus transfer of NF-κB and the expressions of MMP9 and ADAMTS5, two key targets of NF-κB/HIF-2α signal pathway. Taken together, this study demonstrated that ICA may increase the vitality of chondrocytes by suppressing the inflammatory injury through the inhibition on NF-κB/HIF-2α signaling pathway. ICA is one effective candidate drug for the treatment of articular cartilage injury.

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.