Circulating adiposity-related microRNAs as predictors of the response to a low-fat diet in subjects with obesity

Recent studies have revealed the critical role of several microRNAs (miRNAs) in energy homeostasis and metabolic processes and suggest that circulating miRNAs can be used as early predictors of weight loss in the design of precision nutrition. Thus, the aim of this study was to investigate circulating adiposity-related miRNAs as biomarkers of the response to two specific weight loss dietary treatments. The expression of 86 miRNAs was investigated in plasma of 78 subjects with obesity randomized to two different diets [moderately high-protein diet (n = 38) and low-fat diet (n = 40)] and in 25 eutrophic controls (BMI ≤ 25 kg/m²). Bioinformatic analyses were performed to explore the target genes and biological pathways regulated by the dysregulated miRNAs. As results, 26 miRNAs were found differently expressed in eutrophic and volunteers with obesity. Moreover, 7 miRNAs (miR-130a-3p, miR-142-5p, miR-144-5p, miR-15a-5p, miR-22-3p, miR-221-3p and miR-29c-3p) were differentially expressed between responders and non-responders to a low-fat diet. Furthermore, after adjustment for basal glucose levels, 1-SD increase in miR-22-3p expression was associated with reduction in the risk of non-response to low-fat diet [OR = 0.181, 95% CI (0.084-0.947), P = .043]. Bioinformatic analyses evidenced that these 7 miRNAs regulate the expression of genes participating in important metabolic pathways. Conclusively, 7 circulating miRNAs related to adiposity could be used for predicting the response to a low-fat diet intervention prescribed to lose weight.     

Clinical significance of circulating microRNAs as diagnostic biomarkers for coronary artery disease

Coronary artery disease (CAD) is one of the biggest threats to human life. Circulating microRNAs (miRNAs) have been reported to be linked to the pathogenesis of CAD, indicating the possible role in CAD diagnosis. The present study aimed to explore the expression profile of plasma miRNAs and estimate their value in diagnosis for CAD. 67 Non‐CAD control subjects and 88 CAD patients were enrolled. We conducted careful evaluation by RT‐PCR analysis, Spearman rank correlation coefficients analysis, Receiver Operating Characteristic (ROC) curves analysis and so on. The plasma levels of six miRNAs known to be related to CAD were measured and three of them showed obvious expression change. Circulating miR‐29a‐3p, miR‐574‐3p and miR‐574‐5p were all significantly increased. ROC analysis revealed the probability of the three miRNAs as biomarkers with AUCs (areas under the ROC curve) of 0.830, 0.792 and 0.789, respectively. They were significantly correlated with each other in CAD patients, suggesting the possibility of joint diagnosis. The combined AUC was 0.915, much higher than each single miRNA. Therefore, our study revealed three promising biomarkers for early diagnosis of CAD. The combination of these miRNAs may act more effectively than individual ones for CAD diagnosis.     

中期因子在相关疾病发病机制和治疗中的研究进展

中期因子(Midkine,MK),是一种分泌型肝素结合性生长因子,具有促进细胞有丝分裂、诱导细胞恶化、促进微血管生成、抑制细胞凋亡、促进炎症介质趋化、促纤溶等功能特点;经研究发现,当机体处于健康状态时中期因子除了肾脏及小肠上皮少量表达,其他部位极少表达,但机体出现疾病时,中期因子在体内的表达明显增多,如在多种恶性肿瘤、动脉粥样硬化、各类炎症、糖尿病肾病、高血压及COPD等疾病中均监测到中期因子的高表达,进一步研究发现上述疾病的发生发展与中期因子的功能特点密切相关;近年有学者利用MK在疾病发生发展中的功能特点对疾病进行治疗,特别是MK在肿瘤领域的治疗已成为研究热点,本文结合国内外的最新研究现状就MK与相关疾病的发病机制及治疗作一简要概述,并提出进一步研究的设想。     

CD80、CD86在鼻咽癌中的表达及其临床病理意义

目的:研究CD80、CD86在鼻咽癌中的表达变化及其临床病理意义。方法:选择2014年10月至2018年10月本院接诊的鼻咽癌确诊患者64例纳入研究,依据鼻咽癌复发情况分复发组(n=30)和未复发组(n=34);同期选取正常鼻粘膜活检组织33例作为正常对照组,采用SP免疫组化法检测鼻咽癌患者癌组织或正常鼻粘膜活检组织CD80、CD86蛋白的表达,并经Spearman相关性分析法分析CD80、CD86蛋白表达与鼻咽癌恶化程度的相关性。结果:鼻咽癌的癌组织CD80、CD86蛋白均呈高表达,阳性表达主要定位于细胞膜、细胞质,与肿瘤临床TNM分期、淋巴结转移均显著相关(P0.05)。复发组、未复发组肿瘤组织中的mRNA(ARD1、Ptch1、Survivin)表达显著高于对照组,且复发组高于未复发组,差异有统计学意义(P0.05)。Spearman相关性分析显示CD80、CD86蛋白表达与鼻咽癌细胞侵袭能力呈显著正相关(r=0.403、0.547,P0.05)。结论:鼻咽癌的癌组织内CD80、CD86蛋白均呈高表达,与鼻咽癌的临床分期、淋巴结转移及放疗预后关系密切,可能作鼻咽癌临床诊治及预后评估的重要参考指标。     

中老年健康体检人群多项肿瘤标志物筛查结果及与年龄和性别的关系分析

摘要 目的：研究中老年健康体检人群多项肿瘤标志物（TM）筛查结果,分析其与年龄和性别的关系。方法：将自2017年6月至2019年12月于我院接受健康体检的600例中老年体检者纳入研究,分别以流式荧光发光法检测甲胎蛋白（AFP）、癌胚抗原（CEA）、糖类抗原-153（CA-153）、糖类抗原-125（CA-125）水平,并分析不同性别、年龄的体检者上述TM阳性率情况,分析各项TM阳性率检出疾病情况。结果：600例体检者AFP、CEA、CA-153、CA-125水平分别为（17.48±3.84）ng/mL、（4.54±1.19）ng/mL、（29.23±7.10）U/mL、（30.65±6.39）U/mL,阳性率分别为1.67%、4.00%、3.33%、3.83%。男性体检者CEA及CA-153阳性率均高于女性,而CA-125阳性率低于女性（P＜0.05）;男性与女性AFP阳性率对比不明显（P＞0.05）。81～89岁体检者的AFP、CEA、CA-153、CA-125阳性率均高于其他年龄段体检者（P＜0.05）。AFP、CEA、CA-153、CA-125阳性体检者恶性肿瘤检出率较低。结论：AFP、CEA、CA-153、CA-125表达升高,可能是中老年人群肿瘤发生、发展的早期预警,应予以高度重视,且和年龄、性别关系密切。中老年人群定期体检能够早期发现疾病并治疗,防止疾病继续恶化,保证身心健康。     

Urinary metabolomics fingerprinting around parturition identifies metabolites that differentiate lame dairy cows from healthy ones

Lameness is a very important disorder of periparturient dairy cows with implications on milk production and composition as well as with consequences on reproductive performance. The aetiology of lameness is not clear although there have been various hypotheses suggested over the years. The objective of this study was to metabotype the urine of dairy cows prior to, during and after the onset of lameness by evaluating at weeks −8, −4 pre-calving, the week of lameness diagnosis, and +4 and +8 weeks post-calving. We used a metabolomics approach to analyse urine samples collected from dairy cows around calving (6 cows with lameness v. 20 healthy control cows). A total of 153 metabolites were identified and quantified using an in-house MS library and classified into 6 groups including: 11 amino acids (AAs), 39 acylcarnitines (ACs), 3 biogenic amines (BAs), 84 glycerophospholipids, 15 sphingolipids and hexose. A total of 23, 36, 40, 23 and 49 metabolites were observed to be significantly different between the lame and healthy cows at −8 and −4 weeks pre-calving, week of lameness diagnosis as well as at +4 and +8 weeks post-calving, respectively. It should be noted that most of the identified metabolites were elevated; however, a few of them were also lower in lame cows. Overall, ACs and glycerophospholipids, specifically phosphatidylcholines (PCs), were the metabolite groups displaying the strongest differences in the urine of pre-lame and lame cows. Lysophosphatidylcholines (LysoPCs), although to a lesser extent than PCs, were altered at all time points. Alterations in urinary AA concentrations were also observed during the current study for four time points. During the pre-calving period, there was an observed elevation of arginine (−8 week), tyrosine (−8 week) and aspartate (−4 week), as well as a depression of urinary glutamate (−4 weeks). In the current study, it was additionally observed that concentrations of several sphingomyelins and one BA were altered in pre-lame and lame cows. Symmetric dimethylarginine was elevated at both −8 weeks pre-calving and the week of lameness diagnosis. Data showed that urinary fingerprinting might be a reliable methodology to be used in the future to differentiate lame cows from healthy ones.     

Alterations of lymphocyte count and platelet volume precede cerebrovascular lesions in stroke-prone spontaneously hypertensive rats

Abstract

Background: Cerebral small vessel disease (CSVD) is associated with future stroke. Although pathological alteration in small vessels of patients with CSVD can be detected by neuroimaging, diagnosis of CSVD is delayed because it is an asymptomatic disease. The stroke-prone spontaneously hypertensive rat (SHRSP) show similar pathological features to human CSVD and develop stroke-related symptoms with advancing age.

Objective: We investigated the time course of haematological parameters in Wistar rats and SHRSP.

Material and Methods: Blood cells were analysed using an automated haematological analyser.

Results: SHRSP develop stroke-related symptoms including onset of neurological symptoms, decreased body weight and blood brain barrier leakage between 12 and 14?weeks of age. Lymphocyte counts were gradually decreased at 3?weeks before development of stoke-related symptoms and then were further decreased after the development of stroke-related symptoms. The both mean platelet volume and large platelet ratio gradually increased at 3?weeks before the development of stoke-related symptoms. However, although SHRSP showed more microcytic red cells than Wistar rats, the trajectories of change in erythrocyte-related parameters were similar between Wistar rats and SHRSP.

Conclusion: Our pilot study suggests that alterations of lymphocyte count and platelet volume predictive indicators for asymptomatic CSVD and symptomatic stroke in SHRSP.     

Prospects for incorporation of epigenetic biomarkers in human health and environmental risk assessment of chemicals

Epigenetic mechanisms have gained relevance in human health and environmental studies, due to their pivotal role in disease, gene × environment interactions and adaptation to environmental change and/or contamination. Epigenetic mechanisms are highly responsive to external stimuli and a wide range of chemicals has been shown to determine specific epigenetic patterns in several organisms. Furthermore, the mitotic/meiotic inheritance of such epigenetic marks as well as the resulting changes in gene expression and cell/organismal phenotypes has now been demonstrated. Therefore, epigenetic signatures are interesting candidates for linking environmental exposures to disease as well as informing on past exposures to stressors. Accordingly, epigenetic biomarkers could be useful tools in both prospective and retrospective risk assessment but epigenetic endpoints are currently not yet incorporated into risk assessments. Achieving a better understanding on this apparent impasse, as well as identifying routes to promote the application of epigenetic biomarkers within environmental risk assessment frameworks are the objectives of this review. We first compile evidence from human health studies supporting the use of epigenetic exposure‐associated changes as reliable biomarkers of exposure. Then, specifically focusing on environmental science, we examine the potential and challenges of developing epigenetic biomarkers for environmental fields, and discuss useful organisms and appropriate sequencing techniques to foster their development in this context. Finally, we discuss the practical incorporation of epigenetic biomarkers in the environmental risk assessment of chemicals, highlighting critical data gaps and making key recommendations for future research within a regulatory context.     

Free and kerogen‐bound biomarkers from late Tonian sedimentary rocks record abundant eukaryotes in mid‐Neoproterozoic marine communities

Lipid biomarker assemblages preserved within the bitumen and kerogen phases of sedimentary rocks from the ca. 780–729 Ma Chuar and Visingsö Groups facilitate paleoenvironmental reconstructions and reveal fundamental aspects of emerging mid‐Neoproterozoic marine communities. The Chuar and Visingsö Groups were deposited offshore of two distinct paleocontinents (Laurentia and Baltica, respectively) during the Tonian Period, and the rock samples used had not undergone excessive metamorphism. The major polycyclic alkane biomarkers detected in the rock bitumens and kerogen hydropyrolysates consist of tricyclic terpanes, hopanes, methylhopanes, and steranes. Major features of the biomarker assemblages include detectable and significant contribution from eukaryotes, encompassing the first robust occurrences of kerogen‐bound regular steranes from Tonian rocks, including 21‐norcholestane, 27‐norcholestane, cholestane, ergostane, and cryostane, along with a novel unidentified C₃₀ sterane series from our least thermally mature Chuar Group samples. Appreciable values for the sterane/hopane (S/H) ratio are found for both the free and kerogen‐bound biomarker pools for both the Chuar Group rocks (S/H between 0.09 and 1.26) and the Visingsö Group samples (S/H between 0.03 and 0.37). The more organic‐rich rock samples generally yield higher S/H ratios than for organic‐lean substrates, which suggests a marine nutrient control on eukaryotic abundance relative to bacteria. A C₂₇ sterane (cholestane) predominance among total C₂₆–C₃₀ steranes is a common feature found for all samples investigated, with lower amounts of C₂₈ steranes (ergostane and crysotane) also present. No traces of known ancient C₃₀ sterane compounds; including 24‐isopropylcholestanes, 24‐n‐propylcholestanes, or 26‐methylstigmastanes, are detectable in any of these pre‐Sturtian rocks. These biomarker characteristics support the view that the Tonian Period was a key interval in the history of life on our planet since it marked the transition from a bacterially dominated marine biosphere to an ocean system which became progressively enriched with eukaryotes. The eukaryotic source organisms likely encompassed photosynthetic primary producers, marking a rise in red algae, and consumers in a revamped trophic structure predating the Sturtian glaciation.     

An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids

PurposeTo develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.MethodsCells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.ResultsSimulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.ConclusionsThe model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.