Gypenoside XVII (GP-17), one of the dominant active components of Gynostemma pentaphyllum, has been studied extensively and found to have a variety of pharmacological effects, including neuroprotective properties. However, the neuroprotective effects of GP-17 against spinal cord injury (ScI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP-17 on motor recovery and histopathological changes following ScI and to elucidate the mechanisms underlying its neuroprotective effects in a mouse model of ScI. Motor recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was detected by the wet/dry weight method. H&E staining was performed to examine the effect of GP-17 on spinal cord damage. Inflammatory response production was assessed by ELISA. candidate miRNAs were identified following the integrated analysis of the Gene Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the expression levels of associated proteins. The results revealed that GP-17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR-21 expression was downregulated following ScI, whereas it was upregulated following the administration of GP-17. The inhibition of miR-21 eliminated the protective effects of GP-17 on ScI-induced neuronal apoptosis and the inflammatory response. In addition, phosphatase and tensin homologue (PTEN), a key molecule in the activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, was identified as a target of miR-21, and PTEN expression was downregulated by GP-17 through miR-21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by ScI, whereas it was re-activated by GP-17 through the regulation of miR-21 in mice with SCI. On the whole, the findings of the present study suggest that GP-17 plays a protective role in ScI via regulating the miR-21/PTEN/AKT/mTOR pathway.

Aquaporins (AQPs) have been found to be associated with a number of diseases. However, the role of AQP-1 in the pathogenesis of osteoarthritis remains unclear. We previously found that AQP-1 expression was upregulated in osteoarthritic cartilage and strongly correlated with caspase-3 expression and activity. The aim of this study was to further investigate the association of AQP-1 expression with chondrocyte apoptosis in a rat model of osteoarthritis, using RNA interference to knock down AQP-1. For this purspose, 72 male Sprague-Dawley rats were randomly assigned to 3 groups as follows: the control group not treated surgically (n=24), the sham-operated group (n=24), and the osteoarthritis group (n=24). Osteoarthritis was induced by amputating the anterior cruciate ligament and medial collateral ligament and partially excising the medial meniscus. Chondrocytes from the rats with osteoarthritis were isolated and cultured. shRNAs were used to knock down AQP-1 expression in the cultured chondrocytes. The expression of AQP-1 and caspase-3 was determined by reverse transcription-quantitative polymerase chain reaction. Caspase-3 activity was measured using a caspase-3 colorimetric assay. The rats in our model of osteoarthritis exhibited severe cartilage damage. The knockdown of AQP-1 decreased caspase-3 expression and activity in the cultured chondrocytes. In addition, the expression of AQP-1 positively correlated with caspase-3 expression and activity. Thus, the findings of our study, suggest that AQP-1 promotes caspase-3 activation and thereby contributes to chondrocyte apoptosis and to the development of osteoarthritis.

Background: The tumor microenvironment (TME) has an essential role in tumorigenesis, progression, and therapeutic response in many cancers. Currently, the role of TME in acute myeloid leukemia (AML) is unclear.This study investigated the correlation between immune-related genes and prognosis in AML patients.Methods: Transcriptome RNA-Seq data for 151 AML samples were downloaded from TCGA database (https://portal.gdc.cancer.gov/), and the immune related genes (irgs) were selected from Immport database.Bioinformatics screening was used to identify irgs for AML, and genes with a critical role in the prognosis of AML were selected for further analysis. To confirm the prognostic role of irgs in AML, we undertook protein-protein interaction (PPI) network analysis of the top 30 interacting genes. We then investigated associations between immune cell infiltration and prognosis in AML patients. Immunohistochemistry was used to validate protein expression levels between AML and normal bone marrow samples. Analysis of the drug sensitivity of the selected gene was then performed. Results:The integrin lymphocyte function-associated antigen 1 (CD11A/CD18; ITGAL/ITGB2) was identified as the key immune-related gene that significantly influenced prognosis in AML patients.Overexpression of ITGB2 indicated poor prognosis in AML patients (P=0.007). Risk modeling indicated that a high-risk score led to poor outcomes (P=3.076e−08) in AML patients. The risk model showed accuracy for predicting prognosis in AML patients, with area under curve (AUC) at 1 year, 0.816; AUC at 3 years, 0.82; and AUC at 5 years, 0.875. In addition, we found that ITGB2 had a powerful influence on immune cell infiltration into AML TME. The results of immunohistochemistry showed that AML patients had significantly higher ITGB2 protein expression than normal samples. The AML patients were divided into 2 groups based on ITGB2 risk scores. Drug sensitivity test results indicated that the high-risk group was sensitive to cytarabine, axitinib, bosutinib, and docetaxel, but resistant to cisplatin and bortezomib.Conclusions: In the present study, we found that ITGB2 may be able to serve as a biomarker for assessing prognosis and drug sensitivity in AML patients.

Osteoporosis and diabetes have become serious health problems worldwide. Previous studies have suggested that diabetes is associated with osteoporosis and increased fracture risk. However, the mechanism underlying diabetes‑induced osteoporosis remains to be elucidated. Therefore, the present study aimed to examine the mechanism underlying diabetes‑induced osteoporosis, and determine the protective effects of zinc, which is known to be closely associated with osteoporosis and diabetes. The results of the present study demonstrated that zinc inhibited advanced glycation end product (AGE)‑induced MC3T3‑E1 cell apoptosis by attenuating the production of reactive oxygen species, inhibiting caspase‑3 and caspase‑9 activation, and inhibiting the release of cytochrome c from between the mitochondria and the cytosol. Furthermore, zinc was found to protect cells against AGE‑induced apoptosis via the mitogen‑activated protein kinase/extracellular signal‑regulated kinase and phosphoinositide 3‑kinase/AKT signaling pathways. In conclusion, these findings enable a better understanding of the mechanism underlying diabetes‑induced osteoporosis, and may indicate a novel target for its prevention and treatment.

Femoral head necrosis (FHN) is a clinically progressive disease that leads to overwhelming complications without an effective therapeutic approach. In recent decades, transplantation of mesenchymal stem cells (MSCs) has played a promising role in the treatment of FHN in the initial stage; however, the success rate is still low because of unsuitable cell carriers and abridged osteogenic differentiation of the transplanted MSCs. Biopolymeric-derived hydrogels have been extensively applied as effective cell carriers and drug vesicles; they provide the most promising contributions in the fields of tissue engineering and regenerative medicine. However, the clinical potential of hydrogels may be limited because of inappropriate gelation, swelling, mechanical characteristics, toxicity in the cross-linking process, and self-healing ability. Naturally, gelated commercial hydrogels are not suitable for cell injection and infiltration because of their static network structure. In this study, we designed a novel thermogelling injectable hydrogel using natural silk fibroin-blended chitosan (CS) incorporated with magnesium (Mg) substitutes to improve physical cross-linking, stability, and cell osteogenic compatibility. The presented observations demonstrate that the developed injectable hydrogels can facilitate the controlled delivery of immobilized recombinant human bone morphogenic protein-2 (rhBMP-2) and rat bone marrow-derived MSCs (rBMSCs) with greater cell encapsulation efficiency, compatibility, and osteogenic differentiation. In addition, outcomes of in vivo animal studies established promising osteoinductive, bone mineral density, and bone formation rate after implantation of the injectable hydrogel scaffolds. Therefore, the developed hydrogels have great potential for clinical applications of FHN therapy.