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This study explored the active ingredients and mechanism of Pleurotus placentodes extract (PP-a) in alleviating acute liver injury. According to un-targeted metabolomics analysis, 102 compounds were identified in PP-a, 32 were regarded as active compounds for treating liver injury. PP-a’s targets (203) were observed for liver injury by network pharmacology analysis. Animal tests showed that PP-a significantly reduce inflammatory factors, increase anti-oxidative effects, and repair injured liver tissues, further effectively improving liver function. In addition, the mRNA expression of PTGS2 and NR3C1 was significantly reduced, while the mRNA expression of PPARA was significantly increased in CCl4-induced mice as a result of PP-a. These results suggest that P. placentodes exerts hepatoprotective effects probably by regulating the mRNA expression of PTGS2, NR3C1 and PPARA. For PP-a, L-Histidine, N-Acetyl-D-alloisoleucine, 15-OxoEDE and palmitic acid probably play a critical role in protecting against liver injury in CCl4-indcued mice.

Abstract Purpose To establish a multivariate linear equation to predict the diameter (outer diameter) of the acetabular prosthesis used in total hip arthroplasty. Methods A cohort of 258 individuals who underwent THA at our medical facility were included in this study. The independent variables encompassed the patients' height, weight, foot length, gender, age, and surgical access. The dependent variable in this study was the diameter of the acetabular prosthesis utilized during the surgical procedure. The entire cohort dataset was randomly partitioned into a training cohort and a validation cohort, with a ratio of 7:3, employing the SPSS 26.0 software. Pearson correlation analysis was conducted to examine the relationships between the patients' height, weight, foot length, gender, age, surgical access, and the diameter of the acetabular prosthesis in the training cohort. Additionally, a multiple linear regression equation was developed using the independent variables from the training cohort and the diameter of the acetabular prosthesis as the dependent variable. This equation aimed to predict the diameter of the acetabular prosthesis based on the patients' characteristics. The accuracy of the equation was evaluated by substituting the data of the validation cohort into the multiple linear equation. The predicted acetabular prosthesis diameters were then compared with the actual diameters used in the operation. Results The correlation analysis conducted on the training cohort revealed that surgical access (r = 0.054) and age (r = −0.120) exhibited no significant correlation with the diameter of the acetabular prosthesis utilized during the intraoperative procedure. Conversely, height (r = 0.687), weight (r = 0.654), foot length (r = 0.687), and sex (r = 0.354) demonstrated a significant correlation with the diameter of the acetabular prosthesis used intraoperatively. Furthermore, a predictive equation, denoted as Y (acetabular prosthesis diameter in mm) = 20.592 + 0.548 × foot length (cm) + 0.083 × height (cm) + 0.077 × weight (kg), was derived. This equation accurately predicted the diameter within one size with an accuracy rate of 64.94% and within two sizes with an accuracy rate of 94.81%. Conclusion Anthropometric data can accurately predict the diameter of acetabular prosthesis during total hip arthroplasty.

Osteosarcoma is the most common bone cancer in children and adolescents. Tissue inhibitors of metalloproteinases (TIMPs)-3 inhibit matrix metalloproteinases to limit extracellular matrix degradation. Cisplatin is a widely used chemotherapeutic drug used to cure osteosarcoma. Interleukin (IL)-6 and TIMP3 play important roles in the drug resistance of osteosarcoma; however, their relationship in this process remains unclear. This study aimed to explore the role of TIMP3 in the cisplatin sensitivity of osteosarcoma and its underlying molecular mechanisms in vitro and in vivo. We compared TIMP3 expression levels between patients with cisplatin-sensitive and -insensitive osteosarcoma. TIMP3 was overexpressed or knocked down in the Saos2-lung cell line, which is a Saos2 subtype isolated from pulmonary metastases that has higher cisplatin chemoresistance than Saos2 cells. IL-6 expression, cell proliferation, sensitivity to cisplatin, migration, and invasion after TIMP3 overexpression or knockdown were determined. The same experiments were performed using MG63 and U2OS cells. Subsequently, luciferase-labeled Saos2-lung cells overexpressing TIMP3 were injected into the tibiae of nude mice treated with cisplatin. The results showed that IL-6 inhibited TIMP3 expression in Saos2 and Saos2-lung cells via signal transducer and activator of transcription 3 (STAT3) activation. STAT3 knockdown reversed the effect of IL-6. The expression of TIMP3 was higher in patients with cisplatin-sensitive osteosarcoma than in those with insensitive osteosarcoma. IL-6 expression was downregulated upon TIMP3 overexpression, and upregulated by TIMP3 knockdown. TIMP3 overexpression suppressed cell proliferation and enhanced cisplatin sensitivity by activating apoptosis-related signal pathways and inhibiting IL-6 expression in vitro and in vivo. In conclusion, cisplatin sensitivity correlated positively with TIMP3 expression, which is regulated by the IL-6/TIMP3/caspase pathway. The TIMP3 pathway could represent a target for new therapies to treat osteosarcoma.

The aim of this study was to investigate the roles and potential mechanisms of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in the proliferation, migration, and invasion of Ewing's sarcoma cells. RT-qPCR was used to detect the expression of TUG1, microRNA-199a-3p (miR-199a-3p), and musashi2 (MSI2) in Ewing's sarcoma tissues and cell lines. Kaplan-Meier overall survival curves showed the survival rates of Ewing's sarcoma patients with high and low expression of TUG1. The association between the expressions of TUG1/MSI2 and miR-199a-3p in Ewing's sarcoma tissues was assessed by Pearson's correlation analysis. Cell proliferation, migration, and invasion were detected by CCK-8 assay and Transwell assay, respectively. The protein level of MSI2 was determined using western blotting. The interaction between TUG1/MSI2 and miR-199a-3p was validated by the dual-luciferase reporter assay. The levels of TUG1 and MSI2 were increased, while the level of miR-199a-3p was decreased in Ewing's sarcoma tissues and cells. High expression of TUG1 or MSI2 indicated a decreased overall survival rate of Ewing's sarcoma patients. TUG1/MSI2 level was negatively correlated with miR-199a-3p level. While TUG1 level was positively correlated with MSI2 level. In Ewing's sarcoma cells, knockdown of TUG1/MSI2 or overexpression of miR-199a-3p inhibited cell proliferation, migration, and invasion, whereas the overexpression of TUG1/MSI2 presented the opposite results. TUG1 functioned as a competing endogenous RNA to regulate MSI2 expression by sponging miR-199a-3p. Finally, miR-199a-3p inhibitor or MSI2 overexpression counteracted the TUG1 knockdown-mediated inhibitory effect on Ewing's sarcoma cell proliferation, migration, and invasion. TUG1 promotes proliferation, migration, and invasion of Ewing's sarcoma cells via sequestering miR-199a-3p to enhance the MSI2 expression, suggesting that TUG1 might be a potential target for treating Ewing's sarcoma. [ABSTRACT FROM AUTHOR]

Periodontitis is an inflammatory disease characterized by loss of connective tissue and alveolar bone, and osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture. To date, the association between periodontitis and osteoporosis has remained to be fully elucidated. In the present study, an experimental rat model of periodontitis was used to explore the effects of oestrogen deficiency-induced osteoporosis on the maxillary alveolar bone. Forty-four female, six-month-old Sprague-Dawley rats were randomly divided into four groups: Control, ligature, ovariectomized (OVX), and OVX + ligature. One month after ovariectomy, rats in the ligature and OVX + ligature groups received ligatures on their first and second maxillary molars for 1 month. Fluorescent labelling was performed prior to sacrificing the animals. At the end of the experiment, the maxillae and serum were collected and subjected to micro-computed tomography analysis, confocal laser-scanning microscopic observation, Van Gieson's fuchsin staining, tartrate-resistant acid phosphatase staining and ELISA. Ligatures slightly reduced the alveolar bone mineral density (BMD) and bone formation rate, but significantly reduced alveolar crest height (ACH). Ovariectomy reduced the alveolar BMD, impaired the trabecular structure, reduced the bone formation rate and increased the serum levels of bone resorption markers. Animals in the OVX + ligature group exhibited a lower alveolar BMD, a poorer trabecular structure, a reduced ACH, a lower bone formation rate and higher serum levels of bone resorption markers compared with those in the control group. The results of the present study showed that ovariectomy enhanced alveolar bone loss and reduced the ACH of rats with experimental periodontitis. Thus, post-menopausal osteoporosis may influence the progression of periodontitis. [ABSTRACT FROM AUTHOR]

Background Periodontitis is an inflammatory disease characterized by the loss of connective tissue and alveolar bone. There is an increasing evidence that periodontitis is associated with a number of chronic disease, including osteoporosis. Periodontitis and osteoporosis are both bone destructive diseases and of high prevalence in adult population. Osteoporosis could increase some inflammatory factors that also participate in the progression of periodontitis, so as to facilitate the alveolar bone resorption. Simvastatin, specific inhibitor of 3-hydroxy-3- methylglutaryl-coenzyme reductase, is of pleiotropic effects including anti-catabolic andanabolic effect on bone metabolism. This study aimed to explore the local and systemic effect of simvastatin on maxillary in rats with both osteoporosis and periodontitis. Methods Thirty-six 4-month-old female Sprague Dawley rats were randomly assigned to six groups: sham group, ligature group, ovariectomized (OVX) + ligature group, local simvastatin administration to OVX + ligature rats (local simvastatin group), oral simvastatin administration to OVX + ligature rats (oral simvastatin group), local and oral simvastatin administration to OVX + ligature rats (L&O simvastatin group). One month after OVX, ligatures were placed on the maxillary first (M1) and second molars (M2) for 4 weeks on all rats except those in the sham group, followed by simvastatin treatment for 2 months. The maxillae, serum, and femurs were collected for further examination including microcomputed (micro-CT) tomography, hematoxylin and eosin (H&E) staining, tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assays (ELISA), and the three-point bending test. Results Local simvastatin administration increased alveolar crest height and prevented local alveolar bone loss without alteration of systemic bone loss. Oral administration prevented local and systemic bone loss with no effect on alveolar crest height. Conclusions Our results indicate that simvastatin has the potential of promoting bone formation and reducing alveolar bone loss in maxillary following ovariectomy (OVX) and ligature placement in rats. [ABSTRACT FROM AUTHOR]