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Purpose: Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored. Methods: The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell-crystal adhesion were examined in the presence of Laminarin polysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions. Results: Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP. Conclusions: SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal-cell adhesion interactions and the risks of kidney stone formation.
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Background: Due to a lack of related research, we aimed to determine the effectiveness of a pharmacist-led medication reconciliation intervention in China. Methods: We conducted a multicentre, prospective, open-label, assessor-blinded, cluster, nonrandomised controlled study at six county-level hospitals, with hospital wards serving as the clusters. We included patients discharged from the sampled hospitals who were aged ≥60 years; had ≥1 studied diagnoses; and were prescribed with ≥3 medications at discharge. Patients in the intervention group received a pharmacist-led medication reconciliation intervention and those in the control group received standard care. We assessed the incidence of medication discrepancies at discharge, patients' medication adherence, and health care utilisation within 30 days after discharge. Results: There were 429 patients in the intervention group (mean age = 72.5 years, standard deviation (SD) = 7.0) and 526 patients in the control group (mean age = 73.6 years, SD = 7.1). Of the 1632 medication discrepancies identified at discharge, fewer occurred in the intervention group (1.9 per patient on average) than the control group (2.6 per patient on average).The intervention significantly reduced the incidence of medication discrepancy by 9.6% (95% confidence interval (CI) = -15.6, -3.6, P = 0.002) and improved patients' medication adherence, with an absolute decrease in the mean adherence score of 2.5 (95% CI = -2.8, -2.2, P < 0.001). There was no significant difference in readmission rates between the intervention and control groups. Conclusions: Pharmacist-led medication reconciliation at discharge from Chinese county-level hospitals reduced medication discrepancies and improved patients' adherence among patients aged 60 years or above, though no impact on readmission after discharge was observed. Registration: ChiCTR2100045668.
Subject(s)
Medication Reconciliation , Pharmacists , Humans , Aged , Prospective Studies , Hospitals, County , Medication AdherenceABSTRACT
Cancer-associated fibroblasts (CAFs) are significantly involved in determining the patient's prognosis and response to bladder cancer (BLCA) therapy. CAFs can induce epithelial-mesenchymal transformation (EMT) as well as complex interaction with immune cells. Hence, it is imperative to identify potential markers for enhancing our understanding of CAFs in BLCA progression and immune regulation. A variety of algorithms and analyses were employed in the study, leading to the development of a novel prognostic feature for CAFs-Stromal-EMT (CSE)-prognostic feature. This feature was constructed based on the genes MFAP5, PCOLCE2, and JUN. Furthermore, we revealed that patients with higher CSE risk scores responded to immunotherapy better compared to those with lower. Finally, we verified two CSE-related genes using in vitro experiments. Our results suggested that the CSE-prognostic feature could predict the prognosis and evaluate the response of patients to immune and chemotherapies. This would aid clinicians in designing treatment strategies for patients with BLCA.
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Purpose: The crystal adhesion caused by the damage of renal tubular epithelial cells (HK-2) is the key to the formation of kidney stones. However, no effective preventive drug has been found. This study aims to explore the recovery effects of four Laminaria polysaccharides (SLPs) with different sulfate (-OSO3-) contents on damaged HK-2 cells and the difference in the adhesion of damaged cells to nanometer calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) before and after recovery. Methods: Sodium oxalate (2.6 mmol/L) was used to damage HK-2 cells to establish a damaged model. SLPs (LP0, SLP1, SLP2, and SLP3) with -OSO3- contents of 0.73%, 15.1%, 22.8%, and 31.3%, respectively, were used to restore the damaged cells, and the effects of SLPs on the adhesion of COM and COD, with a size of about 100 nm before and after recovery, were measured. Results: The following results were observed after SLPs recovered the damaged HK-2 cells: increased cell viability, restored cell morphology, decreased reactive oxygen levels, increased mitochondrial membrane potential, decreased phosphatidylserine eversion ratio, increased cell migration ability, reduced expression of annexin A1, transmembrane protein, and heat shock protein 90 on the cell surface, and reduced adhesion amount of cells to COM and COD. Under the same conditions, the adhesion ability of cells to COD crystals was weaker than that to COM crystals. Conclusions: As the sulfate content in SLPs increases, the ability of SLPs to recover damaged HK-2 cells and inhibit crystal adhesion increases. SLP3 with high -OSO3- content may be a potential drug to prevent kidney stones.
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Objective: This study aimed to investigate the growth of calcium oxalate (CaOx) crystals regulated by Auricularia auricular polysaccharides (AAPs) with different viscosity-average molecular weights (Mv), the toxicity of AAP-regulated CaOx crystals toward HK-2 cells, and the prevention and treatment capabilities of AAPs for CaOx stones. Methods: The scavenging capability and reducing capacity of four kinds of AAPs (Mv of 31.52, 11.82, 5.86, and 3.34 kDa) on hydroxyl, ABTS, and DPPH free radicals and their capability to chelate divalent iron ions were detected. AAP-regulated CaOx crystals were evaluated by using zeta potential, thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. The cytotoxicity of AAP-regulated crystals was evaluated through examination of cell viability, cell death, malondialdehyde (MDA) content, and cell surface hyaluronic acid (HA) expression. Results: The in vitro antioxidant activities of the four AAPs were observed in the following order: AAP0 < AAP1 < AAP2 < AAP3. Thus, AAP3, which had the smallest Mv, had the strongest antioxidant activity. AAPs can inhibit the growth of CaOx monohydrate (COM), induce the formation of CaOx dihydrate (COD), and reduce the degree of crystal aggregation, with AAP3 exhibiting the strongest capability. Cell experiments showed the lowest cytotoxicity in AAP3-regulated CaOx crystals, along with the lowest MDA content, HA expression, and cell mortality. In addition, COD presented less cytotoxicity than COM. Meanwhile, the cytotoxicity of blunt crystals was less than that of sharp crystals. Conclusion: AAPs, particularly AAP3, showed an excellent antioxidative capability in vitro, and AAP3-regulated CaOx crystals presented minimal cytotoxicity.