Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1.

This study is to probe into the meaning of serum miR-532-5p in nontraumatic osteonecrosis of the femoral head (ONFH), and a molecular mechanism of miR-532-5p in the development of nontraumatic ONFH. This study enrolled 96 patients diagnosed with nontraumatic ONFH and 96 patients with femoral neck fracture. The levels of miR-532-5p, ABL1, MMP-3, MMP-13, and cleaved-caspase3 were determined. Radiographic progression was assessed by ARCO staging system. Visual analog scale (VAS) and Harris hip score (HHS) were employed for evaluation of the symptomatic severity of nontraumatic ONFH. Cell viability and apoptosis in chondrocytes isolated from clinical samples were investigated with CCK-8 and flow cytometry. The levels of lactic dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) were determined. miR-532-5p was downregulated in tissues and serum of patients with nontraumatic ONFH, negatively related with ARCO staging and VAS, and positively correlated with HHS. Cell apoptosis, LDH, MDA, and ROS strengthened, while cell viability, ΔΨm, and SOD reduced in chondrocytes of nontraumatic ONFH patients. ABL1 was upregulated in cartilage tissues from nontraumatic ONFH patients. miR-532-5p targeted ABL1, and overexpressed miR-532-5p alleviated nontraumatic ONFH-induced oxidative stress damage of chondrocytes by restraining ABL1. miR-532-5p ameliorated oxidative stress injury in nontraumatic ONFH by inhibiting ABL1.

Numerical simulation and fast method for the 0D-1D multi-scale coupled model and its application in ischemic brain tissue blood flow problems.

As living standards rise, more and more people are paying attention to their own health, especially issues such as cerebral thrombosis, cerebral infarction, and other cerebral blood flow problems. An accurate simulation of blood flow within cerebral vessels has emerged as a crucial area of research. In this study, we focus on microcirculatory blood flow in ischemic brain tissue and employ a 0D-1D geometric multi-scale coupled model to characterize this process. Given the intricate nature of human cerebral vessels, we apply a numerical method combining the finite element method and the third-order Runge-Kutta method to resolve the coupled model. To enhance computational efficiency, we introduce a fast method based on the reduced-order extrapolation algorithm. Our numerical example underscores the stability of the method and convergence accuracy to O h 3 + τ 3 $$ O\left({h}^3+{\tau}^3\right) $$ , while significantly improving the accuracy and efficiency of blood flow simulation, making the mechanism analysis more accurate. Additionally, we present examples detailing variations and distribution of intracranial pressure and blood flow in ischemic brain tissue throughout a cardiac cycle. Both reduced vascular compliance and vascular stenosis can have adverse effects on intracranial cerebral pressure and blood flow, leading to insufficient local oxygen supply and negative effects on brain function. Meanwhile, there will also be corresponding changes in volume flow and pulsatile blood pressure.

Paeonol inhibits inflammatory response and protects chondrocytes by upregulating sirtuin 1.

Paeonol is the bioactive component in Paeonia lactiflora Pall., Cynanchum paniculatum and Paeonia × suffruticosa Andr. Paeonol has been previously demonstrated to inhibit the release of tumor necrosis factor α (TNF-α) and interluekin 6 (IL-6) in chondrocytes. Sirtuin 1 (SIRT1) is downregulated in degraded cartilage and paeonol could induce nuclear accumulation of SIRT1. Therefore, the present study aims to investigate the possible role of paeonol in chondrocyte inflammation and cartilage protection in osteoarthritis (OA) as well as its regulation of SIRT1. Primary chondrocytes from rat knee joints were transfected with short hairpin (sh) - SIRT1 and (or) paeonol prior to IL-1ß exposure, and then inflammatory response, apoptosis, and extracellular matrix (ECM) degradation in the cells were evaluated concurrent with the activation of the nuclear factor κß (NF-κß) signaling pathway. Increased levels of TNF-α, IL-17, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 along with decreased tissue inhibitor of metalloproteinases 1 and type II collagen levels were found in IL-1ß-stimulated chondrocytes. Chondrocyte apoptosis was elevated and the NF-κß signaling pathway was activated in response to IL-1ß treatment. Paeonol enhanced SIRT1 expression to inactivate the NF-κß signaling pathway, thereby ameliorating inflammatory cytokine secretion, ECM degradation, and chondrocyte apoptosis. In conclusion, the results of the present study confirm the potential of paeonol as a candidate OA drug.

Combined use of intravenous and topical tranexamic acid in patients aged over 70 years old undergoing total hip arthroplasty.

PURPOSE: The present study was designed to evaluate the efficacy and safety of combined use of intravenous (IV) TXA administration and topical intraarticular tranexamic acid (TXA) strategy in patients aged over 70 undergoing total hip arthroplasty (THA). METHODS: One hundred eighty patients were randomized into three groups, including an IV group, a local group, and a combined group. Patients were administrated with 15 mg/kg of IV-TXA in the IV group, 2 g TXA in the topical group, or 15 mg/kg IV-TXA combined with 2 g TXA in the combined group. Total blood loss (TBL), maximum hemoglobin drop, the transfusion rate and the number of allogeneic blood units, and the incidence of deep venous thrombosis (DVT), and pulmonary embolism (PE) were recorded and analyzed. RESULTS: TBL was 757.75 ± 188.95 mL in the combined group, which was significantly lower than in the IV group (892.75 ± 218.47) or the topical group (1015.75 ± 288.71) (p = 0.015, p = 0.001 respectively). The mean values of maximum hemoglobin drop in the combined, IV, and topical groups were 2.67 ± 0.42, 3.28 ± 0.52, and 3.75 ± 0.62 g/dL, respectively, with a significant intergroup difference (p < 0.001 for all). PE was not detected within 1 month after the surgery. Asymptomatic DVT was reported in 1 patient of the IV group, and in 2 patients from the combined group, while the difference was not statistically significant. CONCLUSIONS: Compared to intravenous or topical use of TXA, the combined therapy effectively decreased total blood loss and reduced the transfusion rate, simultaneously possessed the same degree of safety in primary THA patients aged over 70.

Linc01230, transcriptionally regulated by PPARγ, is identified as a novel modifier in endothelial function.

Evidence is growing that PPARγ could improve the bioavailability of NO in pathological conditions to maintain endothelial function by activating Akt/eNOS pathway. LincRNAs participate in regulating development of cardiovascular diseases. Although investigations have been made to delineate the function of PPARγ and lincRNAs, little is known about the regulation relationship between them, especially in endothelial cells. In this study, we not only verified that PPARγ could antagonize the adverse effects brought from ox-LDL, but also found a novel factor related to PPARγ, named linc01230. According to our study, PPARγ transcriptionally regulated linc01230 by specifically combining with two binding regions, which have superposition effect, in the upstream of linc01230 promoter. In addition, linc01230 reduced ox-LDL induced endothelial dysfunction and affected the phosphorylation of Akt. These results conclude linc01230 as a novel modifier in PPARγ-mediated activation of Akt in endothelial function.

Protective effect of an extract of Guipi Pill against radiation-induced damage in mice.

OBJECTIVE: To study the protective effect of an extract of Guipi Pill () against radiation-induced damage. METHODS: A total of 100 Kunming mice were randomly divided into normal group, model group, positive drug group (treated with radioprotective agent "523", 5 mg/kg at 24 h before irradiation) and two treatment groups, with 20 mice in each group. The extract of water extraction-alcohol precipitation (WAP) from Guipi Pill were administered orally to the mice in the two treatment groups at the dose of 500 and 1,000 mg/kg, respectively, for 6 days prior to whole body radiation (8 Gy). Fifty mice with 10 in each group were used to observe the survival rate 30 days after radiation. The other 50 mice with 10 in each group were sacrificed on day 10 after radiation (6 Gy) in order to take blood, liver and unilateral femur. RESULTS: Pretreatment prior to irradiation with WAP resulted in a significantly higher 30-day survival rate of mice after exposure to a potentially lethal dose of 8-Gy radiation. WAP could significantly increase the total white blood cell count and DNA content of bone marrow, and it also increased the activity of various antioxidant enzymes, such as superoxide dismutase, catalase, total antioxidant capacity and glutathione peroxidase in liver tissue of mice, which were reduced by radiation treatment. Maleic dialdehyde level and bone marrow micronucleus rate were significantly reduced by WAP, which were increased after 6-Gy radiation. CONCLUSION: WAP of Guipi Pill could increase the 30-day survival rate and the antioxidant capacity as well as protect bone marrow in mice. WAP of Guipi Pill is an effective radioprotective agent.