Integration of Bioinformatics and Machine Learning to Identify CD8+ T Cell-Related Prognostic Signature to Predict Clinical Outcomes and Treatment Response in Breast Cancer Patients.

The incidence of breast cancer (BC) continues to rise steadily, posing a significant burden on the public health systems of various countries worldwide. As a member of the tumor microenvironment (TME), CD8+ T cells inhibit cancer progression through their protective role. This study aims to investigate the role of CD8+ T cell-related genes (CTRGs) in breast cancer patients. METHODS: We assessed the abundance of CD8+ T cells in the TCGA and METABRIC datasets and obtained CTRGs through WGCNA. Subsequently, a prognostic signature (CTR score) was constructed from CTRGs screened by seven machine learning algorithms, and the relationship between the CTR score and TME, immunotherapy, and drug sensitivity was analyzed. Additionally, CTRGs' expression in different cells within TME was identified through single-cell analysis and spatial transcriptomics. Finally, the expression of CTRGs in clinical tissues was verified via RT-PCR. RESULTS: The CD8+ T cell-related prognostic signature consists of two CTRGs. In the TCGA and METABRIC datasets, the CTR score appeared to be negatively linked to the abundance of CD8+ T cells, and BC patients with higher risk score show a worse prognosis. The low CTR score group exhibits higher immune infiltration levels, closely associated with inhibiting the tumor microenvironment. Compared with the high CTR score group, the low CTR score group shows better responses to chemotherapy and immune checkpoint therapy. Single-cell analysis and spatial transcriptomics reveal the heterogeneity of two CTRGs in different cells. Compared with the adjacent tissues, CD163L1 and KLRB1 mRNA are downregulated in tumor tissues. CONCLUSIONS: This study establishes a robust CD8+ T cell-related prognostic signature, providing new insights for predicting the clinical outcomes and treatment responses of breast cancer patients.

Aerobic exercise improves adipogenesis in diet-induced obese mice via the lncSRA/p38/JNK/PPARγ pathway.

Adipogenesis is one of the triggers of obesity, which is a risk factor for various metabolic diseases. Long noncoding RNA steroid receptor RNA activator (lncRNA-SRA) is closely related to adipogenesis and p38/JNK mitogen-activated protein kinase mediates lipid production by regulating peroxisome proliferator-activated receptor gamma (PPARγ). Aerobic exercise can be efficient in improving adiposity and losing weight. Hence, we hypothesize that aerobic exercise ameliorates obesity by affecting the SRA/p38/JNK/PPARγ pathway and downstream target genes. The broad approaches used to test hypotheses are as follows. Spectrophotometer detected C57BL/6J mice blood lipid level; hematoxylin and eosin-stained fat tissue to check the grade of epididymis fat; quantitative polymerase chain reaction and Western blot detected messenger RNA expression and protein levels. Injected lncRNA-SRA virus vector to overexpress SRA. After 8 weeks of aerobic exercise intervention, obese mice showed significant improvements in body weight, white fat weight, lipid levels, and the Lee index. Aerobic exercise significantly inhibited the expression of SRA, activated the p38/JNK signaling pathway, further inhibited the expression of PPARγ and downstream target genes, and improved obesity. Aerobic exercise intervention improved lipid metabolism in obese mice, and the mechanism may be related to the regulation of the LncSRA/p38/JNK/PPARγ signaling pathway.

Virtual reality combined with robot-assisted gait training to improve walking ability of children with cerebral palsy: A randomized controlled trial.

BACKGROUND: Children with cerebral palsy (CP) have disorders of posture and movement and which can limit physical activities such as walkingOBJECTIVE: This study aims to investigate the effectiveness of virtual reality (VR) combined with robot-assisted gait training (RAGT) on walking ability in children with CP and clarify the most effective degree of weight reduction. METHODS: Sixty CP children were recruited and randomly allocated into four different groups. The control group received conventional physical therapy (n= 15), and task groups performed VR combined with RAGT with 15% (Group A, n= 15) /30% (Group B, n= 15) /45% (Group C, n= 15) weight loss. All participants were given 50 min of therapy per session four times a week for 12 weeks and were assessed pre-and post-test with the surface electromyography (EMG), the Modified Ashworth Scale, the Gross Motor Function Measure (GMFM) dimension E and D, and Six-Minute Walking Test (6-MWT). RESULTS: All indicators had improved significantly in each group after the intervention (P< 0.05). The result of our study demonstrated that the more effective impacts of VR combined with RAGT on walking ability compared to the control group (P< 0.05), and 30% of weight loss had the best improvement in CP children (P< 0.01). CONCLUSIONS: VR combined RAGT can effectively improve walking ability in children with CP, especially when the weight loss is 30%.

Aerobic exercise promotes the expression of ATGL and attenuates inflammation to improve hepatic steatosis via lncRNA SRA.

The role of aerobic exercise in preventing and improving non-alcoholic fatty liver has been widely established. SRA is a long non-coding RNA, which has received increasing attention due to its important role in lipid metabolism. However, it is unclear whether aerobic exercise can prevent and treat hepatic lipid accumulation via SRA. The mice were randomly divided into four groups as follows, normal control group, normal aerobic exercise group, high-fat diet group (HFD), and high-fat diet plus aerobic exercise (8 weeks, 6 days/week, 18 m/min for 50 min, 6% slope) group (HAE). After 8 weeks, the mice in the HAE group showed significant improvement in hepatic steatosis. Body weight as well as blood TC, LDL-C, and liver TG levels were significantly lower in the HAE group than in the HFD group. Compared with the HFD group, the expression of SRA was markedly suppressed and the expression of ATGL was significantly increased in the HAE group. Additionally, the JNK/P38 signaling was inhibited, the pro-inflammatory factors were down-regulated, and the anti-inflammatory factor was increased. In addition to this, the same results were shown in experiments with overexpression of SRA. The results of this study provided new support for aerobic exercise to improve hepatic lipid metabolism via lncRNA.

Improvement of hyperlipidemia by aerobic exercise in mice through a regulatory effect of miR-21a-5p on its target genes.

Hyperlipidemia is a risk factor for cardiovascular disease, and miR-21a-5p plays an important role in the occurrence and progression of hyperlipidemia. Here, we aimed to investigate the mechanism of aerobic exercise improved hyperlipidemia through enhancing miR-21a-5p expression. In this study, high-fat/high-cholesterol diet mice received 8 weeks of aerobic exercise intervention, then we collected plasma and liver samples, we found that there had a notable improvement in weight gain, blood lipid level, and liver steatosis in hyperlipidemia mice after 8 weeks of aerobic exercise intervention. Besides, aerobic exercise significantly up-regulated the expression of miR-21a-5p and provoked favorable changes in the expression of target genes. Knockdown of miR-21a-5p resulted in dysregulation of lipid metabolism and increased expression of FABP7, HMGCR, ACAT1, and OLR1. While aerobic exercise could alleviate miR-21a-5p knock-down induced lipid metabolism disorder. Taken together, these results demonstrated that aerobic exercise improved hyperlipidemia through miR-21a-5p-induced inhibition of target genes FABP7, HMGCR, ACAT1, and OLR1.

Humanin protects cortical neurons from calyculin A-induced neurotoxicities by increasing PP2A activity and SOD.

BACKGROUND: Humanin (HN) is an extensive neuroprotective peptide. This study aims to investigate the neuroprotective effects of HN on Calyculin A (CA)-induced neurotoxicities in cortical neurons and the underlying mechanism. METHODS: CA was added into the cultured cortical neurons to induce neurotoxicity. Cortical neurons were preincubated with HN which plays a protective role. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and Calcein-AM were applied to evaluate the neural insults. Caspase 3 signal and Tunnel were performed to test neural apoptosis. Western blot analysis was used to detect the expressions of phosphorylated tau. The corresponding kits were used to measure the contents of malondialdehyde (MDA) and superoxide dismutase (SOD), and the activity of PP2A, respectively. RESULTS: HN preincubation preserved cell viability, protected the neurons, alleviated oxidative stress, and reserved PP2A activity. It also blocked tau overphosphorylation at Ser199/202, Ser396, and Thr231 sites and protected neurons against CA-induced insults. CONCLUSION: These results suggest that HN may serve as a potential therapeutic agent to prevent the pathological changes induced by CA via modulating the activity of PP2A and oxidative stress in neurodegenerative diseases.

Comparison of the Quenching Effects of Two Main Components of Ziziphi Spinosae Semen on Serum Albumin Fluorescence.

Swertisin (6-glucosyl flavonoid) and spinosin (2″-ß-O-glucopyranosyl swertisin) are two main components from Ziziphi Spinosae Semen, with anti-anxiety and hypnosis effects. The paper aims to compare the differences between the two compounds binding with serum albumins (BSA and HSA). Swertisin and spinosin statically quench intrinsic fluorescence of serum proteins by binding to proteins to form complexes. The fluorescence quenching rates of BSA induced by swertisin or spinosin are faster than those of HSA resulted by swertisin or spinosin, respectively. Each serum protein has only one binding site respectively accessible to the two compounds. Hydrophobic force and hydrogen bond play the important roles during the biding process of swertisin with proteins, but van der Waals force and hydrogen bond are major driving forces for spinosin binding to proteins. Synchronous fluorescence data show that spinosin binds to BSA and HSA and thus changes Tyr and Trp residue microenvironments, and has a greater effect on the latter. Compared with swertisin, spinosin has a stronger effect on the α-helix of proteins. But the distance between swertisin and proteins is slightly closer than spinosin. These findings will contribute to further understand the reaction of Ziziphi Spinosae Semen in the liver phase I oxidation, intestinal hydrolysis and deparaffin metabolism.