Mechanism of non-small cell lung cancer cell-derived exosome miR-196b-5p promoting pyroptosis of tumor T cells and tumor cell proliferation by downregulating ING5.

In the world, lung cancer is one of the most common malignant cancers and has become the leading cause of death of cancers in China, among which non-small cell lung cancer (NSCLC) accounts for a relatively high proportion, but there is a lack of effective treatment at present. An animal model of NSCLC was established, and BEAS-2b, H1299, Lewis, and T cells were used for subsequent experimental verification. The level of miR-196b-5p was detected by quantitative real-time polymerase chain reaction. Growth inhibitor 5 (ING5), CD9, CD63, HSP70, Caspase-1, NLRP3, and GSDMD-NT were detected by western blot. The level of ING5 was confirmed by immunohistochemistry, the location of miR-196b-5p was analyzed by fluorescence in situ hybridization (FISH), cell viability was investigated by Cell Counting Kit-8 kit, and interleukin (IL)-1ß and IL-18 were confirmed by enzyme-linked immunosorbent assay. Cell apoptosis was detected by flow cytometry. In addition, the binding site was verified by dual-luciferase reporter gene experiments. Tumor volume was measured. TUNEL staining was used to detect apoptosis. Flow cytometry was used to measure the levels of CD8 T, CD4 T, and Treg cells in tumors. miR-196-5p was highly expressed in exosomes secreted by tumor cells. miR-196-5p negatively targeted ING5 to promote the growth of tumor cells. Cancer-derived exosomes promote pyroptosis of T cells to further aggravate the development of cancer. Exosome-derived miR-196b-5p promoted pyroptosis of T cells. Exosome-derived miR-196b-5p inhibited the level of ING5 to promote tumor growth and accelerate the process of NSCLC.

The Role of Resveratrol on Spinal Cord Injury: from Bench to Bedside.

Spinal cord injury (SCI) is a severe and disabling injury of the central nervous system, with complex pathological mechanisms leading to sensory and motor dysfunction. Pathological processes, such as oxidative stress, inflammatory response, apoptosis, and glial scarring are important factors that aggravate SCI. Therefore, the inhibition of these pathological processes may contribute to the treatment of SCI. Currently, the pathogenesis of SCI remains under investigation as SCI treatment has not progressed considerably. Resveratrol, a natural polyphenol with anti-inflammatory and antioxidant properties, is considered a potential therapeutic drug for various diseases and plays a beneficial role in nerve damage. Preclinical studies have confirmed that signaling pathways are closely related to the pathological processes in SCI, and resveratrol is believed to exert therapeutic effects in SCI by activating the related signaling pathways. Based on current research on the pathways of resveratrol and its role in SCI, resveratrol may be a potentially effective treatment for SCI. This review summarizes the role of resveratrol in promoting the recovery of nerve function by regulating oxidative stress, inflammation, apoptosis, and glial scar formation in SCI through various mechanisms and pathways, as well as the deficiency of resveratrol in SCI research and the current and anticipated research trends of resveratrol. In addition, this review provides a background for further studies on the molecular mechanisms of SCI and the development of potential therapeutic agents. This information could also help clinicians understand the known mechanisms of action of resveratrol and provide better treatment options for patients with SCI.

Targeted Therapy of Spinal Cord Injury: Inhibition of Apoptosis Is a Promising Therapeutic Strategy.

Spinal cord injury (SCI) is a serious disabling central nervous system injury that can lead to motor, sensory, and autonomic dysfunction below the injury level. SCI can be divided into primary injury and secondary injury according to pathological process. Primary injury is mostly irreversible, while secondary injury is a dynamic regulatory process. Apoptosis is an important pathological event of secondary injury and has a significant effect on the recovery of nerve function after SCI. Nerve cell death can further aggravate the microenvironment of the injured site, leading to neurological dysfunction and thus affect the clinical outcome of patients. Therefore, apoptosis plays a crucial role in the pathological progression of secondary SCI, while inhibiting apoptosis may be a promising therapeutic strategy for SCI. This review will summarize and explore the factors that lead to cell death after SCI, the influence of cross talk between signaling pathways and pathways involved in apoptosis and discuss the influence of apoptosis on SCI, and the therapeutic significance of targeting apoptosis on SCI. This review helps us to understand the role of apoptosis in secondary SCI and provides a theoretical basis for the treatment of SCI based on apoptosis.

Effect and safety of sorafenib in patients with intermediate hepatocellular carcinoma who received transarterial chemoembolization: A retrospective comparative study.

AIM: To evaluate the safety and efficacy of sorafenib plus transarterial chemoembolization (TACE) treatment for intermediate hepatocellular carcinoma (HCC). METHODS: Sixty-seven patients with intermediate-stage [Barcelona Clinic liver cancer stage B (BCLC-B)] HCC who were treated with sorafenib plus TACE or TACE alone between 2009 and 2011 were included in the study. Follow-up was until 2014 or patient death. Two groups were defined in the experiment: The experimental group, treated with sorafenib plus TACE, and the control group, treated with standard TACE alone. RESULTS: The Kaplan-Meier survival analysis showed that the median overall survival (mOS) of the experimental group was 35.2 mo, while that of the control group was 22.0 mo (P < 0.05). Sorafenib plus TACE showed higher incidence rates of rash, hand-foot syndrome (HFS), and hypertension (P < 0.05) than TACE treatment alone. CONCLUSION: Sorafenib plus TACE treatment for BCLC-B HCC significantly prolonged the mOS of patients compared to TACE treatment alone. The most common toxicities with sorafenib were rash (31.6%), HFS (39.5%) and hypertension (31.6%), but there were no intolerable adverse events. The Cox multivariate analysis showed that the survival of patients with BCLC-B HCC depended on the Child-Pugh classification, tumor diameter, and treatment with sorafenib plus TACE compared to TACE alone.

The role of antiangiogenic agents in the treatment of gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The survival of advanced gastric cancer (GC) is dismal, and effects of antiangiogenic agents remain inconclusive. The purpose of this study is to assess combination of chemotherapy with antiangiogenic therapy versus traditional chemotherapy. METHODS: To achieve the goal of scientific rigor, statistics from both referenced works and experiments were analyzed. We carefully searched for the referenced works by retrieving, as well as analyzing, literature databases for information on antiangiogenic therapy compared to other therapeutic approaches used to treat GC patients. Two groups were defined in the experiment: experimental and control groups. The experimental group was treated with antiangiogenic drug, and the control group was treated with standard chemotherapy or placebo. RESULTS: The study included a total of 3240 participants. Overall, there was significant improvement in overall survival (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.67-0.91, P = 0.002), progression-free survival (HR 0.65, 95% CI: 0.52-0.81, P = 0.0002), objective response rate (risk ratio [RR] = 1.58, 95% CI: 1.33-1.88, P < 0.00001), and disease control rate (RR 2.44, 95% CI: 1.57-3.78, P < 0.0001) in the group with antiangiogenic drug versus the group with standard chemotherapy or placebo. Moreover, this new treatment approach showed tolerable toxicity. CONCLUSION: This study confirms the superior efficacy of combination therapy with antiangiogenic agents in comparison to traditional chemotherapy regimens for patients with GC. Moreover, this new treatment approach showed tolerable toxicity. This meta-analysis provides important information for clinicians who are interested in using antiangiogenic therapies to treat GC patients.