BackgroundThis study aimed to investigate the therapeutic effect of low, medium, and high concentrations of medical ozone on trauma-induced lumbar disc herniation.Material/MethodsA total of 80 patients were included and were grouped into a control group, a low medical ozone (20 μg/ml) group, a medium medical ozone (40 μg/ml) group, and a high medical ozone (60 μg/ml) group. The CT scan and enzyme-linked immunosorbent assay (ELISA) were used to detect IL-6 level, SOD activity, IgM, and IgG levels upon admission and at 6 and 12 months after follow-up. The area under the ROC curve (AUC) was calculated for visual analogue scale (VAS) and efficiency rate.ResultsAll patients showed disc retraction at 6- and 12-month follow-up; while patients in the medium medical ozone (40 μg/ml) group showed the greatest disc retraction rate. The IL-6, IgM, IgG, and VAS levels significantly decreased while SOD activity increased among all groups over time (p<0.05). The AUCIL-6, AUCIgG, AUCIgM, and AUCSOD was closest to 1 in the medium medical ozone (40 μg/ml) group compared with other groups (p<0.01), with the highest efficacy at 6 (35%) and 12 (85%) months during follow-up.ConclusionsLow concentrations of medical ozone (20 μg/ml and 40 μg/ml) reduced the serum IL-6, IgG, and IgM expression, presenting as analgesic and anti-inflammatory effects, while high concentrations of medical ozone (60 μg/ml) increased the serum IL-6, IgG, IgM expression, presenting as pain and pro-inflammatory effects.The medical ozone concentration of 40 μg/ml showed the optimal treatment efficacy.

Highlights Differential expression analysis showed a total of 304 differentially expressed genes, which were mainly related to proteoglycans in cancer, the PI3K/Akt signaling pathway, and the TGF-beta signaling pathway. The survival-related linear risk assessment model consisting of eight genes (FERMT2, ITGA5, ITGB1, MCAM, CEMIP, HGF, TGFBR1, F2RL2) was constructed. The survival rates of high-risk patients were significantly lower than that of the low-risk group, and the 3-, 5-, and 10-year AUCs were satisfactory. BMP2, BMPR2 , and GREM1 were differentially expressed in both data sets of breast cancer bone metastasis. In GSE20685 and GSE45255, significant differences in immune infiltration patterns were found between high- and low-risk groups. BMP-2 may regulate the immune infiltration process in breast cancer tissues through the PI3K/Akt signaling pathway.

Breast cancer is the most common cancer among women and accounts for 30% of all female malignancies worldwide. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that exhibit multiple characteristics including differentiation capacity, self-renewal and therapeutic resistance. Recently, BCSCs have attracted attention due to their modulation of breast tumor behaviors and drug resistance. miRNAs are small noncoding mRNAs involved in virtually all biological processes, including stem cell development, maintenance and differentiation. In breast cancer, miRNAs appear to be multi-faceted since they can act as either suppressors or oncogenes to regulate breast cancer progression. This review summarizes the critical roles of miRNAs in regulating multiple signaling pathways such as Wnt/β-catenin, Notch, PI3K/AKT/mTOR, BMI-1 and STAT3 that are important for the BCSC maintenance.

BackgroundUbiquitin-conjugating enzyme variant UEV1A is required for Ubc13-catalyzed K63-linked poly-ubiquitination that regulates several signaling pathways including NF-κB, MAPK and PI3K/AKT. Previous reports implicate UEV1A as a potential proto-oncogene and have shown that UEV1A promotes breast cancer metastasis through constitutive NF-кB activation. Ubc13-Uev1A along with TARF6 can also ubiquitinate AKT but its downstream events are unclear.MethodsIn this study, we experimentally manipulated UEV1 expression in two typical breast cancer cell lines MDA-MB-231 and MCF7 under serum starvation conditions and monitored AKT activation and its downstream protein levels, as well as cellular sensitivity to chemotherapeutic agents.ResultsWe found that overexpression of UEV1A is sufficient to activate the AKT signaling pathway that in turn inhibits FOXO1 and BIM expression to promote cell survival under serum starvation conditions and enhances cellular resistance to chemotherapy. Consistently, experimental depletion of Uev1 in breast cancer cells inhibits AKT signaling and promotes FOXO1 and BIM expression to reduce cell survival under serum starvation stress and enhance chemosensitivity.ConclusionsUev1A promotes cell survival under serum starvation stress through the AKT-FOXO1-BIM axis in breast cancer cells, which unveals a potential therapeutic target in the treatment of breast cancers.

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Background It is imperative to preoperatively distinguish dural ossification (DO) and thus anticipate the risks and outcome of the surgery for patients with ossification of ligamentum flavum (OLF). However, studies have disagreed as to the efficacy of the radiographic signs or factors to predict DO and surgical outcome. In additon, the association between the cerebrospinal fluid cross-section area ratio (CCAR) and DO or clinical outcome had not been reported. The purpose of this study was to analyse CCAR and its role in prediction of DO and neurological function recovery rate in patients with OLF. Methods Fifty-two consecutive patients with OLF, who underwent posterior thoracic decompression and fusion between September 2012 and March 2019 at a single institution, were retrospectively reviewed. Demographic data, radiographic signs of DO, CCAR, pre- and postoperative modified Japanese Orthopedic Association (mJOA) score were recorded. Results There were 27 patients in the DO group and 25 patients in the non-DO group, with a mean age at surgery of 57.4 years and 53.9 years, respectively. No significant differences were found in sex, age, segment of maximum compression and preoperative mJOA score between the two groups. The receiver operating characteristic curve showed that the value of CCAR had a relatively high value for diagnosis of DO and prediction of neurological function recovery rate (P = .000). According to the value of CCAR, three zones were defined as DO zone (≤14.3%), non-DO zone (≥44.5%), and gray zone (14.3 to 44.5%). When the value of CCAR≤14.3%, the recovery rate was poor or fair, while it had good or excellent recovery when CCAR≥45.2%. Conclusion The value of CCAR had a high diagnostic value for prediction of DO and neurological function recovery rate in patients with OLF.

Background/Aims: Currently, scientists attempt to improve outcome of spinal cord injury (SCI) via reducing secondary injury during SCI. Oxidative stress is critical for pathophysiology of secondary damage, thus we mainly focused on the anti-oxidant effects of Lycium barbarum polysaccharides (LBPs) on PC-12 and SH-SY5Y cells as well as the underlying mechanisms. Methods: Oxidative stress was induced by H₂O₂ stimulation. Effects of LBPs on cell viability, apoptosis, and expression of proteins associated with apoptosis and autophagy in H₂O₂-induced cells were assessed by CCK-8 assay, flow cytometry assay and Western blot analysis, respectively. Then, expression of miR-194 was determined by qRT-PCR. Expression of miR-194 was dysregulated, and whether LBPs affected H₂O₂-treated cells through modulating miR-194 was verified. The expression of key kinases in the PI3K/AKT pathway and the intracellular levels of ROS and NO were testified by Western blot analysis and flow cytometry with fluorescent probes. Results: H₂O₂-induced decrease of cell viability and increases of apoptosis and autophagy in PC-12 cells were mitigated by LBPs treatment. Next, we found that miR-194 expression was both down-regulated by LBPs treatment in PC-12 and SH-SY5Y cells. More experiments consolidated that influence of LBPs on H₂O₂-treated cells was reversed by miR-194 overexpression while was augmented by miR-194 inhibition. LBPs elevated the phosphorylated levels of PI3K and AKT and reduced levels of ROS and NO through miR-194. Conclusion: LBPs alleviated H₂O₂-induced decrease of cell viability, and increase of apoptosis and autophagy through down-regulating miR-194. Moreover, LBPs activated the PI3K/AKT pathway and reduced oxidative stress through miR-194.

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