RPS15A Mediates PI3K/AKT Signaling-Induced Parathyroid Cell Proliferation in Rats with Secondary Hyperparathyroidism.

OBJECTIVE: Ribosomal protein S15A (RPS15A) has been identified as a new oncogene in several tumors, but its functional role in secondary hyperparathyroidism (SHPT) characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation remains unclear. METHODS: A rat model of SHPT was successfully established with a high-phosphorus diet plus 5/6 nephrectomy. ELISA assay was used to determine PTH, calcium and phosphorus and ALP activity. Cell proliferation was analyzed by Cell counting Kit-8 (CCK-8) assay. Flow cytometry assay was utilized to determine cell cycle distribution and apoptosis in parathyroid cells. LY294002, an inhibitor of PI3K/AKT signaling, was used to elucidate the relationship between RPS15A and PI3K/AKT signaling. Immunohistochemical (IHC) staining, quantitative real time PCR and western blot analysis were applied to determine related molecular levels. RESULTS: Our data showed an upregulation of RPS15A and activated PI3K/AKT signaling pathway in the parathyroid gland tissues of SHPT rats, accompanied with increased PTH, calcium and phosphorus levels. Knockdown of RPS15A decreased parathyroid cell proliferation, induced cell cycle arrest and apoptosis. Treatment with LY294002 reversed the effects of pcDNA3.1-RPSH15A in parathyroid cells. CONCLUSIONS: Our study demonstrated RPS15A-mediated PI3K/AKT pathway as a novel molecular mechanism in the pathogenesis of SHPT, which may provide a new drug target in the future.

The clinical effectiveness and safety of traditional Chinese medicine uremic clearance granule combined with high-flux hemodialysis in the treatment of uremic pruritus: A protocol for systematic review and meta analysis.

BACKGROUND: Skin pruritus is a common complication in patients with uremia. When the hemodialysis time of patients is extended, and the probability of skin pruritus is greater. Patients often have the symptoms of skin pruritus intolerable, affecting the normal sleep and normal life of patients. The patients with uremic pruritus often constant scratching and pruritus skin, resulting in broken skin, and further symptoms such as infection, and subsequent skin shedding, prurigo nodularis, and other adverse complications, aggravating the patient's condition. Some patients will experience symptoms such as depression and insomnia due to skin pruritus, and simply scratching the skin lead to infection. Severely affected patients may even show suicidal tendency, endangering the physical and mental health of patients, and it is needed to give the effective treatment to patients. Hemodialysis is a common treatment for uremic pruritus, which can effectively relieve the pruritus symptoms of patients. The drugs can also relieve the symptoms and improve the degree of pruritus in patients. And some studies show that traditional Chinese medicine UCG combined with HFH in the treatment of uremic pruritus has a very good effect, Therefore, this study will systematically evaluate the clinical efficacy and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. METHODS: Use computer to search English and Chinese databases, English databases include: PubMed, Web of Science, EMbase, The Cochrane Library. Chinese databases include: CNKI, CBM, WanFang Data and VIP databases, collecting the RCT on the clinical effectiveness and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. The retrieval time is from the beginning of each database to May 1, 2021. In order to improve the retrieval rate of the literature, the references cited in the included research are also collected and screened. Set Chinese and English as the search language. Two members of the research group independently collected, included and excluded the literatures. In case of disagreement, consulting the third party to assist in the judgment. For the literature with missing data, the original author should be contacted as far as possible to obtain complete data. Two evaluators evaluate the bias risk of included studies according to the Cochrane Handbook bias risk assessment tool for RCT. RevMan 5.3 software is used for statistical analysis and the forest plot is drawn to show the outcome indicators and funnel plot is drawn to show the publication bias. RESULTS: This study evaluates the advantages and disadvantages of traditional Chinese medicine UCG combined with HFH and HFH alone in the treatment of uremic pruritus through the clinical effectiveness and safety-related indicators. CONCLUSION: This study will give a positive conclusion on the efficacy and safety of uremic clearance granule in the treatment of uremic pruritus, and the research results will be published in professional journals in the form of academic papers, thus benefiting more patients. ETHICS AND DISSEMINATION: This study belongs to meta-analysis and all data comes from academic papers published publicly in formal academic journals, so there are no ethical issues involved in this study and no ethical review or approval is required. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W8P5G.