Natural small-molecules reverse Xeroderma Pigmentosum Complementation Group C (XPC) deficient-mediated drug-resistance in renal cell carcinoma.

BACKGROUND: Renal cancer is insensitive to radiotherapy or most chemotherapies. While the loss of the XPC gene was correlated with drug resistance in colon cancer, the expression of XPC and its role in the drug resistance of renal cancer have not yet been elucidated. With the fact that natural small-molecules have been adopted in combinational therapy with classical chemotherapeutic agents to increase the drug sensitivity and reduce adverse effects, the use of herbal compounds to tackle drug-resistance in renal cancer is advocated. PURPOSE: To correlate the role of XPC gene deficiency to drug-resistance in renal cancer, and to identify natural small-molecules that can reverse drug-resistance in renal cancer via up-regulation of XPC. METHODS: IHC was adopted to analyze the XPC expression in human tumor and adjacent tissues. Clinical data extracted from The Cancer Genome Atlas (TCGA) database were further analysed to determine the relationship between XPC gene expression and tumor staging of renal cancer. Two types of XPC-KD renal cancer cell models were established to investigate the drug-resistant phenotype and screen XPC gene enhancers from 134 natural small-molecules derived from herbal plants. Furthermore, the identified XPC enhancers were verified in single or in combination with FDA-approved chemotherapy drugs for reversing drug-resistance in renal cancer using MTT cytotoxicity assay. Drug resistance gene profiling, ROS detection assay, immunocytochemistry and cell live-dead imaging assay were adopted to characterize the XPC-related drug resistant mechanism. RESULTS: XPC gene expression was significantly reduced in renal cancer tissue compared with its adjacent tissue. Clinical analysis of TCGA database also identified the downregulated level of XPC gene in renal tumor tissue of stage IV patients with cancer metastasis, which was also correlated with their lower survival rate. 6 natural small-molecules derived from herbal plants including tectorigenin, pinostilbene, d-pinitol, polygalasaponin F, atractylenolide III and astragaloside II significantly enhanced XPC expression in two renal cancer cell types. Combinational treatment of the identified natural compound with the treatment of FDA-approved drug, further confirmed the up-regulation of XPC gene expression can sensitize the two types of XPC-KD drug-resistant renal cancer cells towards the FDA-approved drugs. Mechanistic study confirmed that GSTP1/ROS axis was activated in drug resistant XPC-KD renal cancer cells. CONCLUSION: XPC gene deficiency was identified in patient renal tumor samples, and knockdown of the XPC gene was correlated with a drug-resistant phenotype in renal cancer cells via activation of the GSTP1/ROS axis. The 6 identified natural small molecules were confirmed to have drug sensitizing effects via upregulation of the XPC gene. Therefore, the identified active natural small molecules may work as an adjuvant therapy for circumventing the drug-resistant phenotype in renal cancer via enhancement of XPC expression.

Efficacy of intra-articular polynucleotides associated with hyaluronic acid vs hyaluronic acid alone in the treatment of knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trial.

BACKGROUND: The reduced range of motion and pain are the most characteristic clinical features of osteoarthritis (OA). Hyaluronic acid (HA), which is one of the infiltrative therapies for OA treatment, and polynucleotides (PNs), which is a DNA-derived macromolecule favored cell growth and collagen production, are an ongoing debate in clinical effectiveness. METHODS: We plan to perform a systematic review and meta-analysis of randomized clinical trial to evaluate efficacy of intra-articular polynucleotides associated with hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis. We will search PubMed, EMBASE, Cochrane Library using a comprehensive strategy. The related conference proceedings and reference lists of the included studies will also be checked to identify additional studies. Two reviewers will screen retrieved records, extract information and assess the risk of bias independently. Stata v15.1 software will be used to conduct data synthesis. RESULTS: This study will be submitted to a peer-reviewed journal for publication. CONCLUSION: We hope it will provide a relatively comprehensive reference for clinical practice and future relevant clinical trials. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required, as this study is a systematic review and meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42020167678.

The effects of total hip arthroplasty in treating hip bony fusion in young and middle-aged patients with ankylosing spondylitis.

BACKGROUND: This study aims to investigate the curative effects of total hip arthroplasty (THA) in treating hip bony fusion for young and middle-aged patients with ankylosing spondylitis (AS). METHODS: The clinical data of 26 young and middle-aged patients with AS (31 coxae), who were treated with THA and followed-up for more than 3 years in the period between February 1998 and May 2013, were retrospectively analyzed. Among these patients, 22 patients were male (25 coxae) and 4 patients were female (6 coxae). Patients' age ranged within 19-50 years old, with an average of 31.5 years old. The intervals from arthroplasty to the occurrence of hip joint lesions caused by AS ranged within 2-26 years, with an average of 11.2 years. The average Harris score before the surgery was 19.0 ± 11.5 points. RESULTS: Femoral proximal cleavage fracture occurred in one coxa during the surgery and was fixed by the steel wire cerclage. Sciatic nerve traction injury occurred in one coxa after the surgery, which recovered after 6 months. Posterior hip dislocation occurred in one coxa and was immediately treated with manual reduction. All patients were followed-up, and follow-up duration ranged within 36-123 months, with an average of 46.5 months. In the last follow-up, the average Harris score was 87.1 ± 13.1 points, total passive range of motion was 215.0 ± 22.0°, and passive range of flexion was 90.8 ± 9.3°. All these indexes significantly increased compared with pretreatment (P < 0.01). A periacetabular radiolucent line occurred in one coxa with a width of < 2 mm, and no femoral radiolucent line was found during follow-ups in any patient. Heterotopic ossification occurred in four coxae. CONCLUSION: THA treatment for hip bony fusion caused by AS can achieve satisfactory hip function recovery and excellent prosthesis survival rate.