Oxymatrine inhibits melanoma development by modulating the immune microenvironment and targeting the MYC/PD-L1 pathway.

Oxymatrine, also known as ammothamnine or oxysophoridine, is a natural compound isolated from Sophora flavescens (in Chinese, Kushen), and many previous researchers have characterized its anti-inflammatory, anti-fibrotic and anti-tumor properties. However, the underlying anti-tumor immunological mechanism of oxymatrine remains elusive. In this study, we carried out experiments both in vitro and in vivo and investigated the anti-tumor effect of oxymatrine to inhibit the proliferation and migration of melanoma B16 cells, while promoting apoptosis. Oxymatrine upregulated CD4+ T, CD8+ T and NKT cells, downregulated Treg cells, promoted TNF-α secretion, and successfully modulated the immune microenvironment and ultimately suppressed melanoma development in subcutaneous tumor models established in mice. Evidence from network pharmacology and RNAseq suggested that possible targets of oxymatrine for melanoma treatment included PD-L1 and MYC. We observed oxymatrine inhibited PD-L1 and MYC expression in melanoma cells via qRT-PCR and western blotting analysis, and found MYC potentially regulated PD-L1 to mediate anti-tumor effects. These findings provide insight into the mechanism by which oxymatrine inhibits melanoma and enhances the anti-tumor immune effect. In summary, our study proposes a novel approach to suppress melanoma by targeting the MYC/PD-L1 pathway using oxymatrine, which may develop into a less toxic and more efficient anti-tumor agent for melanoma treatment.

Relationship between irregular diet and risk of esophageal cancer: A meta-analysis.

Background: Associations between irregular diet and the risk of esophageal cancer remain unclear. The current meta-analysis was performed to determine whether the presence of irregular diet increases the risk of esophageal cancer. Methods: The data from PubMed, Cochrane Libraries, and Embase up to 23 January 2022 were included in our analysis to identify studies that investigated associations between irregular diet and the risk of esophageal cancer. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Five cohort studies and one case-control study investigating associations between irregular diet and the risk of esophageal cancer were included. None of the articles demonstrated publication bias. The summary RR was 4.181 (95% CI 2.196-7.960, I2 = 66.1%, p = 0.011). In the subgroup analysis, we found significant heterogeneity in the Non-disease-causing group, nurse group and Asian group. The above three that produce heterogeneity may be the source of heterogeneity in the results of this study. Conclusion: The current meta-analysis indicates that irregular diet increase the risk of esophageal cancer. Trial registration: (https://www.crd.york.ac.uk/prospero/), (PROSPERO, CRD42022306407).

Effects of pericapsular nerve group (PENG) block on postoperative recovery in elderly patients with hip fracture: study protocol for a randomised, parallel controlled, double-blind trial.

INTRODUCTION: Hip fracture is a common and serious emergency in the elderly, and it is associated with severe pain, significant morbidity and mortality. The use of peripheral nerve block can relieve pain effectively and reduce opioid requirements, which may accelerate patient's recovery. The pericapsular nerve group (PENG) block has been found to provide an effective blockade to the hip joint with a potential motor-sparing effect, so we hypothesised that the PENG block may be an effective tool to enhance the recovery in elderly patients after hip fracture surgery. METHODS AND ANALYSIS: This study is a single-centred, randomised, parallel controlled, double-blind trial. A total of 92 elderly patients scheduled for hip fracture surgery will be divided into two groups at random to receive either ultrasound-guided femoral nerve block or ultrasound-guided PENG block. The primary outcome will be to compare the Quality of Recovery-15 scores at 24 hours postoperatively between the two groups. The secondary outcomes will include measuring and comparing the strength of the quadriceps, the visual analogue scale at rest and on movement, the total morphine consumption, the rescue analgesic, the first time of postoperative out-of-bed mobilisation and complications. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Ethics Committee of The First Affiliated Hospital of Guangzhou University of Chinese Medicine on 15 December 2020 (reference K2020-110). The results of this study will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: ChiCTR2100042341.

Tsc1 deficiency impairs mammary development in mice by suppression of AKT, nuclear ERα, and cell-cycle-driving proteins.

Loss of Tsc1/Tsc2 results in excess cell growth that eventually forms hamartoma in multiple organs. Our study using a mouse model with Tsc1 conditionally knockout in mammary epithelium showed that Tsc1 deficiency impaired mammary development. Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium. The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Phosphorylated PDK1 and AKT, nuclear ERα, nuclear IRS-1, SGK3, and cell cycle regulators such as Cyclin D1, Cyclin E, CDK2, CDK4 and their target pRB were all apparently down-regulated in Tsc1(-/-) mammary glands, which could be reversed by rapamycin, suggesting that suppression of AKT by hyperactivation of mTORC1, inhibition on nuclear ERα signaling, and down-regulation of cell-cycle-driving proteins play important roles in the retarded mammary development induced by Tsc1 deletion. This study demonstrated for the first time the in vivo role of Tsc1 in pubertal mammary development of mice, and revealed that loss of Tsc1 does not necessarily lead to tissue hyperplasia.