Neuroprotective effect of tanshinone IIA against neuropathic pain in diabetic rats through the Nrf2/ARE and NF-κB signaling pathways.

The study aims to investigate whether tanshinone (TSN) IIA affects diabetic neuropathic pain (DNP) via the Nrf2/AR and NF-κB signaling pathways. Rats were randomly assigned into DNP group, TSN group (injected with TSN IIA), TSN + DRB group (injected with TSN IIA and 15 mg/kg Nrf2/ARE inhibitors), TSN + PDTC group (injected with TSN IIA and 60 mg/kg NF-κB inhibitors) or control group. The first four groups were successfully established as DNP models after injection of streptozotocin. The blood glucose level, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), nerve conduction velocity (NCV) and antioxidase level were detected. Transmission electron microscopy and toluidine blue staining were utilized to observe the sciatic nerve. RT-qPCR and western blot were used to measure expression levels of Nrf2/ARE and NF-κB signaling pathway-related genes. Blood glucose, malondialdehyde (MDA) and erythrocyte glutathione peroxidase (GSH-Px) levels as well as expression of Keap1 and NF-κB were increased in the TSN, TSN + DRB and TSN + PDTC groups compared to control group. Furthermore, the MWT, TWL, NVC, and superoxide dismutase (SOD) levels and expression of Nrf2, heme oxygenase 1 (HO-1) and inhibitory kappa B (IκB) decreased in the treatment groups. The TSN + DRB and TSN + PDTC groups showed similar trend when compared with the TSN group, while the opposite trend was observed in the TSN group when compared with the DNP group. Our study demonstrates that TSN IIA alleviates neuropathic pain by activating the Nrf2/ARE signaling pathway and inhibiting the NF-κB signaling pathway in diabetic rats.

Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily results in warm, swollen, and painful joints. In this study, we investigate the potentially therapeutic role of artesunate (Art) on chondrocyte proliferation, apoptosis and autophagy in rheumatoid arthritis (RA) via the PI3K/AKT/mTOR signaling pathway. METHODS: Rat model of RA was successfully established through subcutaneous injection of emulsion. Positive protein expression rates of PI3K, AKT and mTOR were determined by immunohistochemistry. RA chondrocytes were initially randomized into five different groups. The mRNA expressions of PI3K, AKT, mTOR, Bcl-2, Bcl-xl, LC3-I, LC3-II and Becline-1 were measured by RT-qPCR. Protein expressions of p-PI3K, p-AKT, p-mTOR, Bcl-2, Bcl-xl, Bax, LC3-I, LC3-II and Becline-1 were determined using western blotting. The chondrocytes of rats with RA and normal rats were isolated and cultured in vitro. Chondrocyte proliferation, apoptosis, cell cycle and autophagy were all determined by CCK-8 assay, flow cytometry and transmission electron microscope (TEM). RESULTS: Artesunate alleviated the inflammation and did not produce any form of hepatotoxicity in rats with RA. In addition, Artesunate decreased expressions of PI3K, AKT, mTOR, p-PI3K, p-AKT, p-mTOR Bcl-2 and Bcl-xl and increased Bax, LC3II/LC3I and Becline-1 protein expression. Artesunate also inhibited chondrocyte proliferation and accelerates cell apoptosis and autophagy via suppression of the PI3K/AKT/mTOR signaling pathway. CONCLUSION: Our study demonstrates that Art inhibits chondrocyte proliferation and accelerates apoptosis and autophagy in RA rats through the PI3K/AKT/mTOR signaling pathway.

Long Noncoding RNA LINC01133 Functions as an miR-422a Sponge to Aggravate the Tumorigenesis of Human Osteosarcoma.

Long noncoding RNAs (lncRNAs) have been verified to participate in various types of malignant tumors, including osteosarcoma (OS), which is the most common primary bone tumor with outstanding morbidity. Although an increasing number of lncRNAs have been reported to mediate the occurrence of OS, the potential mechanisms are still unclear. This study intends to uncover the mechanism by which lncRNA LINC01133 functions as an miRNA sponge to mediate OS tumorigenicity. In this study, we found that the expression level of LINC01133 was statistically upregulated in OS tumor tissue and cell lines compared to noncancerous tissues and a normal human osteoplastic cell line. LINC01133 silencing could also observably suppress the proliferation, migration, and invasion of OS cells (HOS and U2-OS). Bioinformatics analysis predicted that LINC01133 specifically targeted miR-422a, which was validated by dual-luciferase reporter assay. Furthermore, functional experiments revealed that miR-422a played a tumor-suppressive role in OS progression and could effectively reverse the function of LINC01133. In summary, our study discovered that lncRNA LINC01133 aggravates the proliferation, migration, and invasion of OS by sponging miR-422a, which provides a novel insight in the tumorigenesis of OS.

Progress on clinical characteristics and identification of location of thoracic ossification of the ligamentum flavum.

Thoracic ossification of the ligamentum flavum (TOLF) is the most common cause for thoracic spinal stenosis. TOLF is usually complicated by thoracic disc herniation, ossification of the posterior longitudinal ligament and degenerative spinal diseases such as cervical spondylosis and lumbar spinal stenosis, and the ossification also usually has a discontinuous or continuous multi-segment distribution. The resultant superposition of several symptoms makes the clinical manifestations complex. Currently, the diagnosis of TOLF depends mainly on the patient's symptoms, physical examination and thoracic CT and MRI examinations. Identification of the location of TOLF depends more on the doctor's subjective judgement. Diagnostic problems are related to the specific region and level of surgical decompression: if the extent of decompression is insufficient, the treatment is inadequate, resulting in residual symptoms. Obversely, unnecessary trauma and a various complications will occur if the decompression is too extensive. Hence, the clinical features and process of diagnosis, especially the means of identifying the location, still require further improvement. It is necessary to establish a simple and accurate means of identifying the segment of TOLF that is responsible for the neurologic deficit: a number of spinal surgeons have been working hard on this. This article will provided an overview of the clinical features of TOLF and the related problems of clinical identification of the location of the segment causing the neurological deficit. The relationship between the imaging manifestations and clinical characteristics still need to be explored with the aim of establishing a simple and precise method for determining precisely whether TOLF is related to spinal cord injury or not, thus reducing surgical trauma and achieving an optimal prognosis.