Causal role of immune cells in prostate cancer: a bidirectional Mendelian-randomization analyses.

BACKGROUND: Immune cell signatures have been implicated in cancer progression and response to treatment. However, the causal relationship between immune cell signatures and prostate cancer (PCa) is still unclear. This study aimed to investigate the potential causal associations between immune cell signatures and PCa using Mendelian randomization (MR). METHOD: This study utilized genome-wide association studies (GWAS) summary statistics for PCa and immune cell signatures from publicly available datasets. MR analyses, including IVW, MR-Egger, and weighted median methods, were performed to evaluate the causal associations between immune cell signatures and PCa. Multiple sensitivity analysis methods have been adopted to test the robustness of our results. RESULTS: After FDR correction, our findings suggested that specific immune cell signatures, such as HLA DR on CD33+ HLA DR+ CD14dim (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.006), HLA DR on CD33+ HLA DR+ CD14- (OR = 1.32, 95% CI = 1.05-1.67, p = 0.018), and HLA DR on monocyte (OR = 1.23, 95% CI = 1.03-1.47, p = 0.021), were significantly associated with PCa. PCa had no statistically significant effect on immunophenotypes. These results remained robust in sensitivity analyses, supporting the validity of the causal associations. CONCLUSIONS: This study provides evidence of a potential causal relationship between certain immune cell signatures and PCa. We observed that immune cell signatures involving HLA DR expression on specific cell types are associated with an increased risk of PCa.

Effect of music therapy on chemotherapy-induced nausea and vomiting in gastrointestinal cancer: A systematic review and meta-analysis.

BACKGROUND: Chemotherapy is the primary treatment for patients with advanced gastrointestinal cancer, but it has many adverse reactions, particularly nausea and vomiting. Music therapy can reduce anxiety symptoms, avoid the response to the human body under various stress conditions through psychological adjustment, and improve the adverse reactions of chemotherapy. AIM: To investigate the impact of music therapy on relieving gastrointestinal adverse reactions in chemotherapy for patients with digestive tract cancer by meta-analysis. METHODS: EMBASE, PubMed, OVID, WoS, CNKI, CBM, and VIP database were all used for searching relevant literature, and the efficacy after treatment was combined for analysis and evaluation. RESULTS: This study included seven articles. The results of meta-analysis indicated that music therapy could reduce the nausea symptom score of patients after chemotherapy [mean difference (MD) = -3.15, 95% confidence interval (CI): -4.62 to -1.68, Z = -4.20, P < 0.0001]. Music therapy could reduce the vomiting symptom score of patients after chemotherapy (MD = -2.28, 95%CI: -2.46 to -2.11, Z = -25.15, P < 0.0001). Furthermore, music therapy could minimize the incidence of grade I and above nausea or vomiting in patients after chemotherapy (odds ratio = 0.38, 95%CI: 0.26-0.56, Z = -4.88, P < 0.0001). Meta-regression analysis found that publication year was not a specific factor affecting the combined results. There was no significant publication bias (P > 0.05). CONCLUSION: Music therapy can significantly improve the scores of nausea and vomiting symptoms in patients with digestive system cancer during chemotherapy and reduce the incidence of grade I and above nausea and vomiting after chemotherapy, making it an effective psychological intervention method worthy of clinical promotion.

Retinoic acid receptor gamma is required for proliferation of pancreatic cancer cells.

Despite the expectation that retinoic acid receptor could be the potential therapeutic targets for pancreatic cancers, there has been the lack of information about the role and the impact of retinoic acid receptor gamma (RARγ, RARG) on pancreatic cancer, unlike other two RARs. Herein, we applied TCGA and GEO database to show that the expression and prognosis of RARG is closely related to pancreatic cancer, which demonstrates that RARG is commonly overexpressed in human pancreatic cancer and is an independent diagnostic marker predicting the poor prognosis of pancreatic cancer patients. In addition, we demonstrated that the reduction in the expression of RARG in human pancreatic cancer cells dramatically suppress their proliferation and tumor growth in vivo, partially attributable to the downregulation of tumor-supporting biological processes such as cell proliferation, antiapoptosis and metabolism and the decreased expression of various oncogenes like MYC and STAT3. Mechanistically, RARG binds on the promoters of MYC, STAT3, and SLC2A1 which is distinguished from well-known conventional Retinotic acid response elements (RAREs) and that the binding is likely to be responsible for the epigenetic activation in the level of chromatin, assessed by the measurement of deposition of the gene activation marker histone H3 K27 acetylation (H3K27ac) using ChIP-qPCR. In this study, we reveal that RARG plays important role in the tumorigenesis of pancreatic cancer and represents new therapeutic targets for human pancreatic cancer.

Repair of acute liver damage with immune evasive hESC derived hepato-blasts.

Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into hepatic cells, including expandable hepato-blasts (HBs) and hepatocyte-like cells (HLCs) in vitro. Therefore, hESC-derived HBs have the potential to become a renewable cell source for cell therapy of serious liver damage. However, one of the key challenges for such cell therapy is the allogeneic immune rejection of hESC-derived HBs. To overcome this challenge, we developed a strategy to protect the hESC-derived HBs from allogeneic immune rejection by ectopically expressing immune suppressive molecules CTLA4-Ig and PD-L1, denoted CP HBs. Like HBs derived from normal hESCs, CP HBs are capable of repairing liver damage in animal models. Using humanized mice (Hu-mice) reconstituted with human immune system, we showed that CP HBs are protected from allogeneic immune system and can survive long-term in Hu-mice. These data support the feasibility to develop CP HBs into a cell therapy to treat serious liver damage.

Postencephalitis epilepsy in children: Diurnal rhythm of seizures is related to clinical characteristics.

OBJECTIVES: The objective of the study was to summarize the relationship between the clinical features of children with postencephalitis epilepsy and the diurnal rhythm of seizures. METHODS: We collected a retrospective review of 44 patients between 0 and 14 years, who were diagnosed with postencephalitis epilepsy. Patients were divided into three groups by their seizures in day/night or wakefulness/sleep state. RESULTS: Most epileptic seizures of patients of age 3 years or younger occurred during the daytime, and the other occurred most frequently at night. Most epileptic seizures of boys occurred during the wakefulness state, and girls occurred most frequently in sleep. Seizures of patients with the first seizure in the daytime occurred more frequently during the daytime and the wakefulness state; on the contrary, the first seizure in the nighttime occurred more frequently during the nighttime and the sleep state. Tonic seizure occurred more often during the nighttime and in sleep; epileptic spasm occurred more frequently during the daytime and wakefulness. Most seizures of temporal origin occurred in the awakening. The seizures of patient occurred more often during the wakefulness state; the prognosis was worse. Patients with the peak of seizures in the daytime, the level of the physiological development were poorer. CONCLUSIONS: The diurnal rhythm of seizures is different in patients with postencephalitis epilepsy with different clinical characteristics (age, gender, time of first seizure, seizure pattern, electroencephalography (EEG), prognosis, and physiological development). Our results may assist in seizure prediction, individualized treatment patterns, and prognosis prediction.