Inhibition of proinflammatory macrophage responses and lymphocyte proliferation in vitro by ethyl acetate leaf extract from Daphne gnidium

Medicinal plants are considered immunomodulatory as they display various biological activities. There is no report addressing the anti-inflammatory effects of Daphne gnidium. In this study, we investigated the effects of D. gnidium ethyl acetate (EA) leaf extract on mice immune cell function in vitro. Production of pro-inflammatory cytokines (IL-1β and TNF-α), cyclooxygenase-2-derived prostaglandinE2 (PGE2) and iNOS-II-synthesised nitric oxide (NO) were examined. EA extract effect on mitogen-induced lymphocyte proliferation was also investigated. We reported for the first time that D. gnidium EA leaf extract dose-dependently inhibits macrophage proinflammatory function by reducing LPS-induced production of IL-1β, TNF-α, COX-2-derived PGE2 and iNOS-II-synthesised NO. Mitogen-induced lymphocyte proliferation was also dose-dependently inhibited by the extract. Lectin-induced response appears to be more sensitive to the suppressive effects of the extract than LPS-stimulated response. Collectively, these results demonstrate that D. gnidium EA leaf extract acts as an in vitro anti-inflammatory factor by inhibiting mice macrophage and lymphocyte activities.     

Agonist antibody activates death receptor 6 downstream signaling involving TRADD recruitment

Death receptor 6 (DR6) is a member of the death domain-containing receptors that belong to the TNFR superfamily. To date, the ligand for DR6 is still not clearly defined. Here, we developed a functional agonist monoclonal antibody (DQM3) against DR6, which bound to the first cysteine-rich domain. Importantly, DR6 signaling could be clearly activated by DQM3, which was dependent on its intracellular death domain. In addition, we demonstrated that the association between DR6 and TRADD was enhanced upon DQM3 stimulation and TRADD was involved in DR6-induced signaling activation. Taken together, our findings provide new insight into a novel mechanism by which DR6 induces downstream signaling in response to an agonist antibody.     

High-dimensional Cytometry (ExCYT) and Mass Spectrometry of Myeloid Infiltrate in Clinically Localized Clear Cell Renal Cell Carcinoma Identifies Novel Potential Myeloid Targets for Immunotherapy

1. Download : Download high-res image (236KB)
2. Download : Download full-size image

Highlights

• •Using ExCYT, genomics, and Mass Spectrometry, we were able to uncover immune cell marker alterations that provide new insight into the biology of early stage ccRCC.
• •Among the CD45⁺ population, we observed a high level of myeloid cell infiltration in treatment-naïve ccRCC tissues.

     

Involvement of INF-γ functional single nucleotide polymorphism +874 T/A (rs2430561) in breast cancer risk

According Global Cancer Statistics 2020 GLOBOCAN estimates female breast cancer was found as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), and the fourth leading cause (6.9%) of cancer death among women worldwide. Identification of new diagnostic marker sharply characterize the tumor feature is intensive need. The present work was performed to investigate the involvement of the INF-γ + 874 T/A gene polymorphism in different breast cancer prognostic factors. Polymorphism detection analysis was performed on 163 subjects from breast cancer patients, 79 with inflamed cells of breast patients and 144 controls. The gene polymorphism was detected using the amplification refractory mutation system- polymerase chain reaction method (ARMS-PCR). The distribution of INF-γ T + 874A gene polymorphism shows strong significant association between INF-γ + 874 T/A genotypes TT in BC patients (ORTT: 6.41 [95% CI = 2.72–15.1] P < 0.0001) as well as strong significant association regarding T allele (ORT: 1.99 [95% CI = 1.43–2.76] P < 0.0001) when compared to the healthy control. In ICB group the strong association was noted with INF-γ + 874 T/A genotypes AT genotype (ORAT: 2.28 [95% CI = 1.22–4.29] P = 0.007). From the different histological BC hormonal markers the human epidermal growth factor receptor 2 (HER2) was showing significant association in INF-γ + 874 T/A genotypes TT (P = 0.03) and recessive model (TT versus AA + AT P = 0.03). Concerning different BC prognostic models, the poor prognostic one of luminal B, (ER^+ve PR^+ve Her2^+ve) show significant association in the host INF-γ + 874 T/A genotype (TT, P = 0.03) and recessive model (TT versus AA + AT P = 0.02) when compared to the good prognostic hormonal status luminal A model, (ER^+ve PR^+ve Her2-ve). It seems that this is the first study that interested in correlate the INF-γ + 874 T/A gene polymorphisms in Egyptian BC patients. T allele, TT genotype and recessive model of the INF-γ + 874 T/A gene variants were documented as risk factors for BC pathogenesis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.     

腮腺肿瘤患者行游离保留SMAS术后的复发及预后影响因素分析

摘要 目的：探讨腮腺肿瘤患者行游离保留SMAS术后的复发及预后影响因素分析。方法：以我院2016年3月-2022年1月收治的60例腮腺肿瘤患者作为研究对象。所有患者均行游离保留SMAS联合全腮腺切除术治疗。术后进行随访。采用χ²检验和独立样本t检验进行腮腺肿瘤患者预后复发及预后存活情况的亚组分析。采用Pearson检验进行相关性分析;采用Cox回归模型计算腮腺肿瘤患者预后的独立危险因素。结果：复发和未复发患者性别、年龄、BMI、糖尿病病史和高血压病史无显著差异（P＞0.05）;复发和未复发患者的淋巴结转移、病理类型、TNM分期、AJCC临床分期差异显著（P<0.05）;预后死亡和预后存活患者性别、年龄、BMI、糖尿病病史和高血压病史无显著差异（P＞0.05）;预后死亡和预后存活患者的淋巴结转移、病理类型、TNM分期、AJCC临床分期和复发情况差异显著（P<0.05）;淋巴结转移、病理类型、TNM分期、复发、AJCC临床分期与腮腺肿瘤患者预后存活情况密切相关（P<0.05）;多因素Cox分析结果显示,淋巴结转移、病理类型、TNM分期、复发、AJCC临床分期是独立危险因素（P<0.05）。结论：疾病相关因素是导致腮腺恶性肿瘤患者复发和死亡的重要因素,临床早期可针对性调整治疗方案以降低患者术后复发和恶性肿瘤。     

Mechanisms of metastasis: epithelial-to-mesenchymal transition and contribution of tumor microenvironment

Every year about 500,000 people in the United States die as a result of cancer. Among them, 90% exhibit systemic disease with metastasis. Considering this high rate of incidence and mortality, it is critical to understand the mechanisms behind metastasis and identify new targets for therapy. In recent years, two broad mechanisms for metastasis have received significant attention: epithelial-to-mesenchymal transition (EMT) and tumor microenvironment interactions. EMT is believed to be a major mechanism by which cancer cells become migratory and invasive. Various cancer cells--both in vivo and in vitro--demonstrate features of epithelial-to-mesenchymal-like transition. In addition, many steps of metastasis are influenced by host contributions from the tumor microenvironment, which help determine the course and severity of metastasis. Here we evaluate the diverse mechanisms of EMT and tumor microenvironment interactions in the progression of cancer, and construct a rational argument for targeting these pathways to control metastasis.     

肿瘤相关巨噬细胞：在肿瘤演进中的作用及潜在抗肿瘤靶点

炎症是公认的肿瘤十大特征之一,而肿瘤相关巨噬细胞是肿瘤微环境的重要组成部分,它影响肿瘤的生长、血管生成、免疫抑制、 转移和药物抗性。最新研究表明,肿瘤相关巨噬细胞还会影响抗肿瘤治疗的临床疗效。鉴于肿瘤相关巨噬细胞在肿瘤演进中起重要作用, 其作为潜在抗肿瘤靶点备受关注。基于最新的研究,对人类癌症中肿瘤相关巨噬细胞的主要功能、作用和特征以及用作新兴肿瘤治疗干预 靶点作一综述。     

思维导图引导康复锻炼对胸腰椎肿瘤术后功能恢复的干预效果

目的:研究思维导图引导康复锻炼对胸腰椎肿瘤术后功能恢复的干预效果,为患者术后的康复提供指导。方法:选择我院2017年1月-2019年12月期间我院200例胸腰段肿瘤术后患者。按照随机数表法将其分为研究组与对照组。研究组采用思维导图引导康复锻炼措施,对照组采用常规术后康复锻炼措施。比较两组患者干预前后腰背部功能、日常生活活动能力、社会生活生存质量及康复质量的评分结果。结果:干预后研究组生活自理能力、疼痛情况、站立、坐位、步行、睡眠情况、社会生活的Oswestry功能障碍(ODI)指数明显低于对照组,差异有统计学意义(P0.05)。干预后研究组Barthel指数以及Fugl-Meyer评分明显高于对照组,差异有统计学意义(P0.05)。干预后研究组社会功能缺陷筛选量表(SDSS)评分与生存质量测定量表(QOLI)评分明显优于对照组,差异有统计学意义(P0.05)。干预后研究组患者的躯体症状、心理状态及康复状况评分明显高于对照组,差异有统计学意义(P0.05)。结论:思维导图引导康复锻炼对胸腰椎肿瘤术后功能恢复有着较为理想的效果,值得临床推广运用。