人桥本甲状腺炎甲状腺组织中miRNAs表达谱的差异性分析

目的：桥本甲状腺炎是一种自身免疫性甲状腺疾病，且其发病率呈逐年上升趋势，在医疗实践中，HT 被认为是原发性甲状腺 功能减退最常见的原因，同时较易发生甲状腺癌和淋巴瘤。另外，HT 缺乏早期诊断标准，临床上发病隐匿且表现多样，病人多不 易察觉而延误治疗。本文旨在应用microRNA 芯片技术系统筛查HT病变甲状腺组织，以此研究并揭示其HT 的miRNA 表达谱 变化。方法：本研究首先采用microRNA芯片技术，对正常甲状腺组织及桥本甲状腺炎甲状腺组织中microRNA 的表达进行比较， 筛选桥本甲状腺炎中差异性表达的miRNAs。结果：与正常甲状腺相比，在桥本甲状腺炎及其合并甲状腺乳头状癌的一侧桥本甲 状腺炎中分别有39 个和25 个miRNAs 分子发生了差异性表达（P<0.05），比较2 组中共有的miRNAs 发现，miR-142-3p、 miR-338-3p、miR-454、miR-146a、miR-29b-1*、miR-150、miR-223 表达上调，miR-654-5p、miR-601、miR-198、miR-1226* 表达下调 （log2 FC≥ 2，P＜0.05）；而miR-142-5p 在原发性桥本甲状腺炎中表达显著性升高近8 倍（log2 FC=7.959，P＜0.01）。结论：我们通 过microRNA芯片，首次直接系统筛查了桥本甲状腺炎病变组织相关miRNA 表达谱，总体上初步掌握了与正常甲状腺相比，桥 本甲状腺炎及合并甲状腺乳头状癌时其miRNA 表达谱的变化情况，为我们后续的研究提供了方向与基础。     

Splenic gene expression profiling in White Leghorn layer inoculated with the Salmonella enterica serovar Enteritidis

Salmonella enterica serovar Enteritidis (SE) is a foodborne pathogen that can threaten human health through contaminated poultry products. Live poultry, chicken eggs and meat are primary sources of human salmonellosis. To understand the genetic resistance of egg‐type chickens in response to SE inoculation, global gene expression in the spleen of 20‐week‐old White Leghorn was measured using the Agilent 4 × 44 K chicken microarray at 7 and 14 days following SE inoculation (dpi). Results showed that there were 1363 genes significantly differentially expressed between inoculated and non‐inoculated groups at 7 dpi (I7/N7), of which 682 were up‐regulated and 681 were down‐regulated genes. By contrast, 688 differentially expressed genes were observed at 14 dpi (I14/N14), of which 371 were up‐regulated genes and 317 were down‐regulated genes. There were 33 and 28 immune‐related genes significantly differentially expressed in the comparisons of I7/N7 and I14/N14 respectively. Functional annotation revealed that several Gene Ontology (GO) terms related to immunity were significantly enriched between the inoculated and non‐inoculated groups at 14 dpi but not at 7 dpi, despite a similar number of immune‐related genes identified between I7/N7 and I14/N14. The immune response to SE inoculation changes with different time points following SE inoculation. The complicated interaction between the immune system and metabolism contributes to the immune responses to SE inoculation of egg‐type chickens at 14 dpi at the onset of lay. GC, TNFSF8, CD86, CD274, BLB1 and BLB2 play important roles in response to SE inoculation. The results from this study will deepen the current understanding of the genetic response of the egg‐type chicken to SE inoculation at the onset of egg laying.     

Distribution and function of prophage phiRv1 and phiRv2 among Mycobacterium tuberculosis complex

Mycobacterium tuberculosis complex (MTBC) is notorious for causing diseases, such as tuberculosis. Tuberculosis caused by M. tuberculosis remains a global public health concern. Two prophages, phiRv1 and phiRv2, can be found among most MTBC genomes. However, no precise functions have been assigned for the two prophages. In this paper, to find out the function of these two prophages, the distribution and function of phiRv1 and phiRv2 in MTBC genomes were analyzed from multiple omics data. We found that complex insertion, deletion, and reorganization appeared on the locus of two prophages in MTBC genomes; some genes of the two prophages can be translated and are functional from proteomic data; the expression of other prophage genes, such as Rv1577c, Rv2650c, Rv2652c, Rv2659c, and Rv2658c, can vary with environmental stresses and might enhance the fitness of MTBC. These data will facilitate our in-depth understanding of their function.     

Stimulation of HeLa cell growth by physiological concentrations of 4-hydroxynonenal

The aim of this study was to analyze the growth response of HeLa cells over a prolonged period of time to a single exposure of physiological and supraphysiological concentrations of 4-hydroxynonenal (HNE), a peroxidation product of omega-6-polyunsaturated fatty acids. Furthermore, the growth modulating effect of serum factors, particularly albumin, on the growth pattern was examined. The effects of HNE on the growth rate and viability of the cells, as well as on the incorporation of labelled amino acids were monitored daily over a period of four days. Fetal calf serum not only had a growth stimualting effect but also modulated the action of HNE. In neither respect was albumin able to substitute for serum indicating that the influence of serum was not exerted via an albumin–HNE conjugate. HNE had a clear dose-dependent effect and a distinction could be made between a supraphysiological concentration (100 μM), which was primarily cytotoxic and a physiological range (below 10 μM) which showed growth modulatory effects. These effects consisted of a transient inhibition in the initial phase of the cell growth, which under optimal conditions (in presence of serum) was followed by a period of increased proliferation, compared to untreated control cultures, until confluence was attained. It is suggested that HNE is not only a toxic product of lipid peroxidation, but a physiological growth regulating factor as well.     

Synthesis and biological evaluation of glucose conjugated phthalocyanine as a second-generation photosensitizer

Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can’t be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-infrared (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles.     

LncRNA HOXB-AS1 promotes cell growth in multiple myeloma via FUT4 mRNA stability by ELAVL1

Multiple myeloma (MM) is defined as the second most common hematological tumor in the globe. Long noncoding RNAs (lncRNAs) have been reported to play stimulative or suppressive role in the progression of different carcinomas. The investigation of lncRNAs in MM is still inadequate. LncRNA HOXB cluster antisense RNA 1 (HOXB-AS1) was once revealed to facilitate glioma progression by affecting cellular activities of glioma cells. However, whether HOXB-AS1 participates in the development of MM still remains an enigma. In this study, we unveiled that HOXB-AS1 was highly expressed in MM and loss-of-function assays certified that HOXB-AS1 obstruction suppressed MM cell proliferation, and stimulated cell apoptosis. In addition, HOXB-AS1 could modulate fucosyltransferase 4 (FUT4) and FUT4-mediated Wnt/β-catenin pathway. In subsequence, it was observed from mechanism assays that HOXB-AS1 enhanced the interaction between ELAVL1 and FUT4 so as to stabilize FUT4 messenger RNA. In the end, rescue experiments affirmed that HOXB-AS1 affected the cell growth through FUT4 in MM. In conclusion, the whole modulation mechanism of HOXB-AS1/ELAVL1/FUT4 axis in MM was validated in this study, which suggested that HOXB-AS1 might function as a powerful and promising therapeutic biomarker for the clinical treatment of patients with MM.     

N-phenyl ureidobenzenesulfonates,a novel class of promising human dihydroorotate dehydrogenase inhibitors

N-phenyl ureidobenzenesulfonates (PUB-SOs) is a new class of promising anticancer agents inducing replication stresses and cell cycle arrest in S-phase. However, the pharmacological target of PUB-SOs was still unidentified. Consequently, the objective of the present study was to identify and confirm the pharmacological target of the prototypical PUB-SO named 2-ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) leading to the cell cycle arrest in S-phase. The antiproliferative and the cytotoxic activities of SFOM-0046 were characterized using the NCI-60 screening program and its fingerprint was analyzed by COMPARE algorithm. Then, human dihydroorotate dehydrogenase (hDHODH) colorimetric assay, uridine rescuing cell proliferation and molecular docking in the brequinar-binding site were performed. As a result, SFOM-0046 exhibited a mean antiproliferative activity of 3.5 μM in the NCI-60 screening program and evidenced that leukemia and colon cancer cell panels were more sensitive to SFOM-0046. COMPARE algorithm showed that the SFOM-0046 cytotoxic profile is equivalent to the ones of brequinar and dichloroallyl lawsone, two inhibitors of hDHODH. SFOM-0046 inhibited the hDHODH in the low nanomolar range (IC₅₀ = 72 nM) and uridine rescued the cell proliferation of HT-29, HT-1080, M21 and MCF-7 cancer cell lines in the presence of SFOM-0046. Finally, molecular docking showed a binding pose of SFOM-0046 interacting with Met43 and Phe62 present in the brequinar-binding site. In conclusion, PUB-SOs and notably SFOM-0046 are new small molecules hDHODH inhibitors triggering replication stresses and S-phase arrest.