Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Identifying Patients at High Risk of Chronic Pain After Video-Assisted Thoracoscopic Surgery Using Thermal Quantitative Sensory Testing.

OBJECTIVE: To examine whether perioperative thermal quantitative sensory testing could be used to identify patients at high risk of chronic pain after video-assisted thoracoscopic surgery (VATS). DESIGN: A single-center, prospective, observational study. SETTING: At the Peking University People's Hospital. PARTICIPANTS: A total of 111 patients scheduled to undergo VATS were enrolled. INTERVENTIONS: Quantitative sensory testing was conducted at the anterior intercostal incision prior to surgery and after chest tube removal. MEASUREMENTS AND MAIN RESULTS: The patient's chronic pain was assessed at 3 months after surgery using a questionnaire. The incidence of chronic pain was 35 out of 107 evaluable patients (32.7%). Among the 35 patients with chronic pain, 26 had features characteristic of neuropathic pain (74.3%). Compared to the patients without chronic pain, subjects with chronic pain had a significantly greater perioperative change in cold pain threshold (CPT; p = 0.032), but not cold detection threshold, warm detection threshold, and hot pain threshold . In the multivariate regression, perioperative CPT change was associated with chronic pain after VATS (odds ratio = 1.043, p = 0.026). CONCLUSIONS: Chronic pain after VATS is typically neuropathic. The change in perioperative CPT at the incision site may help to identify patients at higher risk of chronic pain after VATS.

microRNA-107 protects against inflammation and endoplasmic reticulum stress of vascular endothelial cells via KRT1-dependent Notch signaling pathway in a mouse model of coronary atherosclerosis.

Coronary atherosclerosis is a long-term, sustained, and evolving inflammatory disease manifested with the remodeling of the coronary arteries. The purpose of this study is to explore the potential role of microRNA-107 (miR-107) in vascular endothelial cells (VECs) in coronary atherosclerosis by regulating the KRT1 gene and the Notch signaling pathway. A mouse model of coronary atherosclerosis was established. The relationship between miR-107 and KRT1 was analyzed and verified by dual-luciferase reporter assay. The functional role of miR-107 in coronary atherosclerosis was determined using ectopic expression and depletion. Blood lipid levels and atherosclerotic index (AI) were measured in atherosclerotic mice. Expression pattern of miR-107, KRT1, Notch signaling pathway, inflammatory/anti-inflammatory factors, and endoplasmic reticulum (ER) stress-related genes was evaluated by means of reverse transcription quantitative polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. Meanwhile, cell-cycle distribution and cell apoptosis in VECs were assessed by flow cytometry. Atherosclerotic mice exhibited higher blood lipid levels, AI, apoptotic index, and KRT1-positive expression as well as inhibited Notch signaling pathway when compared with normal mice. The miR-107 was revealed to bind to KRT1; miR-107 upregulation or KRT1 silencing resulted in reductions in blood lipid levels and AI, inhibition in cell apoptosis, inflammation, and ER stress. Restored miR-107 or downregulated KRT1 activated the Notch signaling pathway. These results supported the notion that miR-107-targeted KRT1 inhibition activated the Notch pathway, thereby, protecting against the coronary atherosclerosis. Findings in this study might provide a novel biomarker for the coronary atherosclerosis treatment.