Effects of Qingshen Granules on Immune Function in Patients with Comorbid Chronic Renal Failure and Damp-Heat Syndrome: A Multicenter, Randomized, Controlled Trial.

OBJECTIVE: The current study sought to compare the effects of the addition of Qingshen granules to conventional Western medicine on immune function in patients with comorbid chronic renal failure and damp-heat syndrome and to explore the possible mechanisms responsible for any differences observed. METHODS: Through a multicenter, randomized, controlled study, a total of 282 eligible patients were divided into experimental (n = 136) and control groups (n = 146). All of the patients were treated with conventional Western medical therapy. The experimental group also received Qingshen granules three times daily for 12 weeks. Clinical efficacy was observed in the two groups. Peripheral blood levels of CD4+ T cells, CD8+ T cells, Th17 cells, nuclear factor-κB p65 (NF-κB p65) activity, serum interleukin-17 (IL-17), serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), tumor necrosis factor receptor-associated factor 6 (TRAF6), fibronectin (FN), and type IV collagen (Col-IV) were detected in both groups. RESULTS: The total clinical curative effective rate was significantly higher (p < 0.05) in the experimental group (79.41%) than in the control group (67.12%). Before treatment, there were no significant differences in CD4+/CD8+ T cell ratio, Th17 cell level, NF-κB p65 activity, serum IL-17, IL-6, TNF-α, TRAF6, FN, and Col-IV between the experimental and control groups (p > 0.05); however, all of the measures were significantly higher than those observed in a healthy comparison group (p < 0.05 or p < 0.01). After treatment, the above indexes in the experimental group were significantly lower than those before treatment (p < 0.05 or p < 0.01). Similarly, NF-κB p65 activity, serum IL-17, TNF-α, TRAF6, FN, and Col-IV in the control group were significantly lower than the levels observed prior to treatment (p < 0.05 or p < 0.01); however, while all of the other indexes were lower than those observed before treatment, the differences were not statistically significant (p > 0.05). CONCLUSION: Qingshen granules adjust immune dysfunction, improve immunity mediated inflammatory response, and attenuate renal fibrosis in patients with comorbid chronic renal failure and damp-heat syndrome.

Living-Cell Imaging of Mitochondrial Membrane Potential Oscillation and Phenylalanine Metabolism Modulation during Periodic Electrostimulus.

Special electrosensory cells are sensitive to electric fields and give responses upon stimulation, but little is known about normal regular cells and cancerous cells. Herein, by designing nucleus- and mitochondria-targeting SERS nanoprobes combined with fluorescent monitoring of the mitochondrial membrane potential (MMP) variations, we found an interesting electrosensory and self-healing response in MMP within cancerous and normal cells during periodic impulse electrostimulation (IES). More importantly, the key regulator role of phenylalanine (phe) was revealed by cell fluorescent imaging and SERS detection, whose expression level was increased in response to IES to induce cell apoptosis. During IES off-state, the self-repair function of cells was activated to reduce phe release. We also found that cancerous cells (MCF-7 and HeLa cells) demonstrated a response more remarkable than that of normal cells (L929 and H8 cells) to periodic IES. Our finding revealed a common electrosensory and self-repair biofunction of cells and its related phe metabolism response. Understanding the difference of biophysical/electrophysiological responses between cancerous and normal cells may broaden the view for cancer therapy in the future.

Smart Plasmonic Nanorobot for Real-Time Monitoring Cytochrome c Release and Cell Acidification in Apoptosis during Electrostimulation.

Cytochrome c (Cyt c) release and cellular pH change are two important mediators of apoptosis. Effective methods to regulate or monitor such two events are therefore highly desired for apoptosis research and cancer cell therapy. Herein, we exploited electrostimulation to regulate cellular Cyt c release and apoptosis process, and by designing and preparing a smart and efficient plasmonic nanorobot (with surface-modified Cyt c-specific aptamer and 4-mercaptobenzoic acid) that is capable of Cyt c capture and self-sensing, we achieved real-time SERS monitoring of dynamic Cyt c release and simultaneous cell acidification in apoptosis during electrostimulation. Distinctly different molecular stress responses in the two events for cancerous MCF-7 and HeLa cells and normal L929 cells were identified and revealed. The method and results are valuable and promising for apoptosis and Cyt c-mediated biology studies.

Nucleus and Mitochondria Targeting Theranostic Plasmonic Surface-Enhanced Raman Spectroscopy Nanoprobes as a Means for Revealing Molecular Stress Response Differences in Hyperthermia Cell Death between Cancerous and Normal Cells.

Metallic plasmonic nanoparticles have been intensively exploited as theranostic nanoprobes for plasmonic photothermal therapy (PPT) and surface-enhanced Raman spectroscopy (SERS) applications. But the underlying molecular mechanisms associated with PPT-induced apoptosis between cancerous and normal cells have remained largely unknown or disputed. In this study, we designed an organelle-targeting theranostic plasmonic SERS nanoprobe (CDs-Ag/Au NS) composed of porous Ag/Au nanoshell (p-Ag/Au NSs) and carbon dots (CDs) for nucleus and mitochondria targeted PPT of cells. The differences in molecular stress response in the PPT-induced hyperthermia cell death between cancerous HeLa and normal L929 and H8 cells have been revealed by site-specific single-cell SERS detection. The contents of tryptophan (Trp), phenylalanine (Phe), and tyrosine (Tyr) in HeLa cells were found more evidently increased than L929 and H8 cells during the PPT-induced cell-death process. And from the mitochondria point of view, we found that the PPT-induced cell apoptosis for HeLa cells mainly stems from (or is regulated through) cellular thermal stress-responsive proteins, while for L929 and H8 cells it seems more related to DNA. Understanding molecular stress response difference of the PPT-induced cell apoptosis between cancerous and normal cells is helpful for diagnosis and treatment of cancer, and the method will open an avenue for single-cell studies.