Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role.

Objective:To investigate the predictive value of circulating miR-143 and miR-182 for the short-term clinical outcomes in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to Danzhou People's Hospital from January 2018 to June 2020 were included prospectively. The modified Rankin Scale was used to evaluate the short-term clinical outcome at 14 d after onset or at discharge. 0-2 was defined as good outcome, and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for poor short-term clinical outcomes in patients with AIS. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of miR-143 and miR-182 for the short-term clinical outcomes in patients with AIS. Results:A total of 158 patients with AIS, aged 65.80±12.36 years, were enrolled, including 105 males (66.46%), 95 patients with good outcome (60.1%) and 63 with poor outcome (39.9%). The age, total cholesterol, triglyceride, low-density lipoprotein cholesterol, baseline National Institutes of Health Stroke Scale (NIHSS) score, serum miR-143 and miR-182 level in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.984, 95% confidence interval [ CI] 1.315-3.617; P=0.036), low-density lipoprotein cholesterol ( OR 2.108, 95% CI 1.406-4.103; P=0.013), baseline NIHSS score ( OR 2.584, 95% CI 1.675-4.505; P=0.005), miR-143 ( OR 3.205, 95% CI 2.370-6.180; P<0.001) and miR-182 ( OR 2.802, 95% CI 1.905-5.516; P<0.001) were the independent risk factors for poor outcomes in patients with AIS. ROC curve analysis showed that the combined area under the curve of miR-143 and miR-182 to predict the poor outcome in patients with AIS was 0.935 (95% CI 0.873-0.992), the sensitivity and specificity were 96.5% and 87.0% respectively. Conclusions:The increase of serum miR-143 and miR-182 was closely associated with the poor short-term outcomes in patients with AIS. The combination of the two has a good predictive value for the poor short-term outcomes in patients with AIS.

Objective:To investigate the predicting value of serum miR-195 and miR-599 for the outcome of patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to Danzhou People's Hospital from January 2018 to July 2020 were enrolled prospectively. The modified Rankin Scale was used to evaluate the outcome of patients at 14 d after onset or when they were discharged from the hospital. A score of 0-2 was defined as a good outcome and a score of >2 were defined as a poor outcome. Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcome of patients with AIS. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive value of serum miR-195 and miR-599 for the poor outcome of patients with AIS. Results:A total of 158 patients with AIS were enrolled. Their age was (65.80±12.36) years old, 105 were males (66.46); 95 patients (60.1%) had a good outcome, and 63 patients (39.9%) had a poor outcome. The age, total cholesterol, triglycerides, low-density lipoprotein cholesterol, baseline National Institutes of Health Stroke Scale (NIHSS) score, serum miR-195 and miR-599 levels in the poor outcome group were significantly higher than those of the good outcome group ( P<0.05). Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.984, 95% confidence interval [ CI] 1.315-3.617; P=0.036), low-density lipoprotein cholesterol ( OR 2.108, 95% CI 1.406-4.103; P=0.013), baseline NIHSS score ( OR 2.584, 95% CI 1.675-4.505; P=0.005), serum miR-195 ( OR 3.927, 95% CI 2.615-8.227; P<0.001) and miR-599 ( OR 2.952, 95% CI 1.973-6.114; P<0.001) were the independent risk factors for the poor outcome of patients with AIS. ROC curve analysis showed that the area under the curve (0.938, 95% CI 0.882-0.997) of serum miR-195 combined with miR-599 for predicting poor outcome was significantly higher than that predicted alone, and its predictive sensitivity and specificity were 97.0% and 87.4% respectively. Conclusions:The higher levels of serum miR-195 and miR-599 are associated with the poor outcome of patients with AIS. The combination of the both had good predictive value for the poor outcome of patients with AIS.

Objective:To investigate the expressions of serum microRNA-24 (miR-24) and microRNA-29b (miR-29b) in elderly patients with acute ischemic stroke (AIS) and their neural function prognostic value.Methods:A prospective study was conducted. 170 elderly patients with AIS admitted to department of neurology of Danzhou People's Hospital from January 1st, 2017 to March 31st, 2019 were enrolled. According to modified Rankin scale (mRS) score, the patients were divided into good neural function prognosis group (mRS score ≤ 2, n = 105) and poor neural function prognosis group (mRS score > 2, n = 65). According to National Institutes of Health stroke scale (NIHSS) score, the patients were divided into mild group (NIHSS score < 5, n = 50), moderate group (NIHSS score 5-20, n = 76) and severe group (NIHSS score > 20, n = 44). Sixty-five healthy volunteers in the same period were enrolled as the control group. The expressions of serum miR-24 and miR-29b were determined by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve was plotted to analyze the value of serum expressions of miR-24 and miR-29b for predicting the poor neural function prognosis of elderly patients with AIS. Pearson correlation was used to analyze the correlation between the expressions of serum miR-24, miR-29b and NIHSS, mRS scores in elderly patients with AIS. Results:The expressions of serum miR-24 and miR-29b in the AIS group were significantly lower than those in the healthy control group [miR-24 (2 -ΔΔCt): 0.64±0.17 vs. 2.18±0.85, miR-29b (2 -ΔΔCt): 0.72±0.21 vs. 3.05±0.96, both P < 0.01]. The expressions of serum miR-24 and miR-29b in the poor neural function prognosis group were significantly lower than those in the good neural function prognosis group [miR-24 (2 -ΔΔCt): 0.20±0.05 vs. 1.16±0.48, miR-29b (2 -ΔΔCt): 0.18±0.03 vs. 1.41±0.56, both P < 0.01]. The expressions of serum miR-24 and miR-29b in the severe group were significantly lower than those in the mild and moderate groups [miR-24 (2 -ΔΔCt): 0.13±0.02 vs. 1.30±0.51, 0.56±0.14; miR-29b (2 -ΔΔCt): 0.09±0.01 vs. 1.52±0.60, 0.62±0.13; all P < 0.01], and they were significantly lower in the moderate group than those in the mild group (all P < 0.01). ROC curve analysis showed that the optimal cut-off values of serum miR-24 and miR-29b expressions for predicting poor neural function prognosis in elderly AIS patients were 0.53 and 0.48, respectively. The area under ROC curve (AUC) of the two combined prognoses was 0.920 [95% confidence interval (95% CI) was 0.861-0.982], and it was significantly higher than that of miR-24 (AUC was 0.802, 95% CI was 0.742-0.860) or miR-29b (AUC was 0.835, 95% CI was 0.778-0.890) alone ( Z values were 6.513 and 4.902, respectively, both P < 0.05), with sensitivity and specificity of 92.0% and 85.7%. Pearson correlation analysis showed that the expressions of serum miR-24 and miR-29b were negatively correlated with NIHSS score ( r values were -0.758 and -0.794, respectively) and mRS score ( r values were -0.817 and -0.860, respectively) in elderly AIS patients (all P < 0.01). Conclusion:The down-regulated expressions of serum miR-24 and miR-29b are correlated with the severity degree of neurological impairment and neural function prognosis of elderly AIS patients, and the two combined have certain value for predicting the neural function prognosis of elderly AIS patients.

Objective: To analyze the risk factors and the predictive value of LDL/HDL ratio in acute ischemic stroke recurrence.
Methods: A total of 143 patients with acute ischemic stroke treated in our hospital were studied. The patients were followed-up for 2 years, the risk factors and the predictive value of LDL/HDL ratio for stroke recurrence were analyzed.
Results: Single factor analysis indicated that lacunar infarction, hypertension, blood pressure, the levels of LDL, HDL, ratio of LDL/HDL, stroke scale score, life ability score were the risk factors of ischemic stroke recurrence. Multivariate analysis presented that hypertension, ratio of LDL/HDL, TG level were the independent risk factors for ischemic stroke recurrence. LDL and ratio of LDL/HDL were positively related to ischemic stroke recurrence, HDL was negatively related to ischemic stroke recurrence, P<0.05. The speciifcity and sensitivity of LDL/HDL for predicting ischemic stroke recurrence were at 81.16%and 95.65%respectively.
Conclusion: The predictive value of LDL/HDL ratio could help us to identify the patients with high risk of ischemic stroke recurrence which is important for the early clinical intervention.