龙葵当归三棱汤治疗卵巢癌临床疗效及对免疫指标及炎性因子的影响

目的探讨龙葵当归三棱汤对卵巢癌患者的临床疗效及免疫指标及炎性因子的影响。方法选取2016年11月-2018年12月60例卵巢癌患者进行研究,随机分为试验组和对照组各30例,对照组采用单纯紫杉醇加顺铂化疗治疗,试验组在对照组的基础上进行龙葵当归三棱汤治疗,比较两组患者的总有效率、血清肿瘤标志物水平[CA125、癌胚抗原(CEA)]变化、以及Th1、Th2、Th1/Th2、调节性T淋巴细胞(Treg)及炎症因子[白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)]及干扰素(INF-γ)和不良反应。结果试验组的总有效率90.0%(27/30)明显高于对照组76.7%(23/30),差异具有统计学意义(P<0.05);试验组CA125、CEA、IL-2、IL-6、INF-γ均明显低于对照组,IL-10明显高于对照组,差异具有统计学意义(P<0.05);试验组的Th1、Th1/Th2均明显高于对照组(P<0.05),试验组的Th2、Treg明显低于对照组(P<0.05);试验组的不良反应率6.7%(2/30)明显低于对照组33.3%(10/30)(P<0.05)。结论龙葵当归三棱汤可以有效的改善卵巢癌的临床疗效,提高患者的免疫力,降低炎性反应和化疗的不良反应。     

Interactions between immune response to fungal infection and microRNAs: The pioneer tuners

Due to their physiological and biological characteristics, numerous fungi are potentially emerging pathogens. Active dynamicity of fungal pathogens causes life-threatening infections annually impose high costs to the health systems. Although immune responses play crucial roles in controlling the fate of fungal infections, immunocompromised patients are at high risk with high mortality. Tuning the immune response against fungal infections might be an effective strategy for controlling and reducing the pathological damages. MicroRNAs (miRNAs) are known as the master regulators of immune response. These single-stranded tuners (18-23 bp non-coding RNAs) are endogenously expressed by all metazoan eukaryotes and have emerged as the master gene expression controllers of at least 30% human genes. In this review article, following the review of biology and physiology (biogenesis and mechanism of actions) of miRNAs and immune response against fungal infections, the interactions between them were scrutinised. In conclusion, miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections. Undoubtedly, advanced studies in this field, further identifying of miRNA roles in governing the immune response, pave the way for inclusion of miRNA-related immunotherapeutic in the treatment of life-threatening fungal infections.     

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.     

Compositional analyses reveal correlations between taxon-level gut bacterial abundance and peripheral T cell marker expression in African infants

ABSTRACT

Although exclusive breastfeeding has been linked to lower rates of postnatal HIV transmission compared to nonexclusive breastfeeding, mechanisms underlying this are unclear. Across a longitudinally sampled cohort of South African infants, we showed that exclusively breastfed (EBF) infants had altered gut bacterial communities when compared to nonexclusively breastfed (NEBF) infants, as well as reduced peripheral CD4 + T cell activation and lowered chemokine and chemokine receptor expression in the oral mucosa. We further demonstrated that the relative abundance of key taxa was correlated with peripheral CD4 + T cell activation. Here, we supplement those findings by using compositional data analyses to identify shifts in the abundance of several Bifidobacteria strains relative to select strains of Escherichia, Bacteroides, and others that are associated with the transition to NEBF. We illustrate that the abundance ratio of these taxa is tightly correlated with feeding modality and is a strong predictor of peripheral T cell activation. More broadly, we discuss our study in the context of novel developments and explore future directions for the field.     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

pH sensing in skin tumors: Methods to study the involvement of GPCRs,acid-sensing ion channels and transient receptor potential vanilloid channels

Solid tumors exhibit an inversed pH gradient with increased intracellular pH (pH_i) and decreased extracellular pH (pH_e). This inside-out pH gradient is generated via sodium/hydrogen antiporter 1, vacuolar-type H + ATPases, monocarboxylate transporters, (bi)carbonate (co)transporters and carboanhydrases. Our knowledge on how pH_e-signals are sensed and what the respective receptors induce inside cells is scarce. Some pH-sensitive receptors (GPR4, GPR65/TDAG8, GPR68/OGR1, GPR132/G2A, possibly GPR31 and GPR151) and ion channels (acid-sensing ion channels ASICs, transient receptor potential vanilloid receptors TRPVs) transduce signals inside cells. As little is known on the expression and function of these pH sensors, we used immunostainings to study tissue samples from common and rare skin cancers. Our current and future work is directed towards investigating the impact of all the pH-sensing receptors in different skin tumors using cell culture techniques with selective knockdown/knockout (siRNA/CRISPR-Cas9). To study cell migration and proliferation, novel impedance-based wound healing assays have been developed and are used. The field of pH sensing in tumors and wounds holds great promise for the development of pH-targeting therapies, either against pH regulators or sensors to inhibit cell proliferation and migration.     

知柏地黄丸对卵巢储备功能低下性激素水平及妊娠结局的影响

目的:分析知柏地黄丸对卵巢储备功能低下(DOR)患者性激素水平级妊娠结局的影响,探究其可能的作用机制。方法:选取2015年1月至2017年1月泸州市中医医院收治的DOR患者104例作为研究对象,按照随机数字表法随机分为对照组(n=53)和观察组(n=51)。对照组采用激素人工周期治疗,观察组在对照组治疗基础上予以知柏地黄丸加减辨证治疗,连续治疗6个月为1个疗程。比较2组患者治疗前、后卵巢血流动力学指标、Treg免疫细胞情况、性激素指标及2组患者随访期内的妊娠结局、药物不良反应。结果:观察组在下调DOR患者的收缩期峰值流速(S)/舒张末期流速(D)值、搏动指数(PI)、阻力指数(RI)基础卵泡刺激素(FSH)、基础雌二醇(E2)、FSH/LH水平方面较对照组更具优势,且在提升患者Treg细胞占比、CD4+T、CD8+T、CD4+T/CD8+T、自然受孕率、辅助生育技术受孕率方面效果更优(均P<0.05);且并未提高患者的药物不良反应率(P>0.05)。结论:知柏地黄丸辅助激素人工周期治疗法加减辨治DOR,可有效提升患者Treg细胞免疫功能,改善卵巢血流动力学水平,降低性激素水平,提升DOR患者妊娠结局水平,且安全性高,具有较高的临床价值。