TRIM27 is an adverse prognostic biomarker and associated with immune and molecular profiles in right-sided colon cancer

Right-sided colon cancer (RCC), as an independent tumor entity, shows a poor prognosis. It is imperative to detect immune microenvironment-related genes for predicting RCC patient prognosis and study their function in RCC. Tripartite motif-containing 27 (TRIM27) was identified as a risk signature from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets by using weighted gene co-expression network analysis, differentially expressed analysis, and univariate Cox analysis. It predicted a poorer overall survival and increased lymph node metastasis, which were then validated in our 48 clinical samples. Using immunohistochemistry, TRIM27 was found to be highly expressed in both cancer cells and surrounding immunocytes, and its expression in tumor or immune cells both predicted a poorer prognosis. Thereafter, the functional mechanism, immune and molecular characteristics of TRIM27 were investigated using gene set enrichment analysis (GSEA), ESTIMATE, CIBERSORT, and gene set variation analysis (GSVA) at the single-cell, somatic mutation, and RNA-seq level. Patients with highly expressed TRIM27 presented lower CD4⁺ T cell infiltration and activation of the mTORC1/glycolysis pathway. In addition, patients with highly expressed TRIM27 were characterized by hypermetabolism, higher tumor purity, more BRAF mutation, and more chromosomal instability. Collectively, TRIM27 is an important immune-related prognostic biomarker in patients with RCC. It may function via activating the mTORC1/glycolysis pathway and suppressing CD4⁺ T cells. These results indicated that TRIM27 could be a promising therapeutic target in RCC.     

Long‐term outcome of cerebral amyloid angiopathy‐related hemorrhage

ObjectThe long‐term functional outcome of cerebral amyloid angiopathy‐related hemorrhage (CAAH) patients is unclear. We sought to assess the long‐term functional outcome of CAAH and determine the prognostic factors associated with unfavorable outcomes.MethodsWe enrolled consecutive CAAH patients from 2014 to 2020 in this observational study. Baseline characteristics and clinical outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long‐term outcome.ResultsAmong the 141 CAAH patients, 76 (53.9%) achieved favorable outcomes and 28 (19.9%) of them died at 1‐year follow‐up. For the longer‐term follow‐up with a median observation time of 19.0 (interquartile range, 12.0–26.5) months, 71 (50.4%) patients obtained favorable outcomes while 33 (23.4%) died. GCS on admission (OR, 0.109; 95% CI, 0.021–0.556; p = 0.008), recurrence of ICH (OR, 2923.687; 95% CI, 6.282–1360730.14; p = 0.011), WML grade 3–4 (OR, 31.007; 95% CI, 1.041–923.573; p = 0.047), severe central atrophy (OR, 4220.303; 95% CI, 9.135–1949674.84; p = 0.008) assessed by CT was identified as independent predictors for long‐term outcome.InterpretationNearly 50% of CAAH patients achieved favorable outcomes at long‐term follow‐up. GCS, recurrence of ICH, WML grade and cerebral atrophy were identified as independent prognostic factors of long‐term outcome.     

Preparation and lithium storage of core–shell honeycomb-like Co3O4@C microspheres

Core–shell honeycomb-like Co₃O₄@C microspheres were synthesized via a facile solvothermal method and subsequent annealing treatment under an argon atmosphere. Owing to the core–shell honeycomb-like structure, a long cycling life was achieved (a high reversible specific capacity of 318.9 mA h g⁻¹ was maintained at 5C after 1000 cycles). Benefiting from the coated carbon layers, excellent rate capability was realized (a reversible specific capacity as high as 332.6 mA h g⁻¹ was still retained at 10C). The design of core–shell honeycomb-like microspheres provides a new idea for the development of anode materials for high-performance lithium-ion batteries.

The reversible specific capacity of CSHCo₃O₄@C microspheres was as high as 332.6 mA h g⁻¹ at 10C, which was significantly higher than that of SCo₃O₄ microspheres (68.7 mA h g⁻¹).     

Discovery of a highly specific 18F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

As a member of cyclic nucleotide phosphodiesterase (PDE) enzyme family, PDE10A is in charge of the degradation of cyclic adenosine (cAMP) and guanosine monophosphates (cGMP). While PDE10A is primarily expressed in the medium spiny neurons of the striatum, it has been implicated in a variety of neurological disorders. Indeed, inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system (CNS) pathologies caused by dysfunction of the basal ganglia–of which the striatum constitutes the largest component. A PDE10A-targeted positron emission tomography (PET) radioligand would enable a better assessment of the pathophysiologic role of PDE10A, as well as confirm the relationship between target occupancy and administrated dose of a given drug candidate, thus accelerating the development of effective PDE10A inhibitors. In this study, we designed and synthesized a novel ¹⁸F-aryl PDE10A PET radioligand, codenamed [¹⁸F]P10A-1910 ([¹⁸F]9), in high radiochemical yield and molar activity via spirocyclic iodonium ylide-mediated radiofluorination. [¹⁸F]9 possessed good in vitro binding affinity (IC₅₀ = 2.1 nmol/L) and selectivity towards PDE10A. Further, [¹⁸F]9 exhibited reasonable lipophilicity (logD = 3.50) and brain permeability (P_app > 10 × 10⁻⁶ cm/s in MDCK-MDR1 cells). PET imaging studies of [¹⁸F]9 revealed high striatal uptake and excellent in vivo specificity with reversible tracer kinetics. Preclinical studies in rodents revealed an improved plasma and brain stability of [¹⁸F]9 when compared to the current reference standard for PDE10A-targeted PET, [¹⁸F]MNI659. Further, dose–response experiments with a series of escalating doses of PDE10A inhibitor 1 in rhesus monkey brains confirmed the utility of [¹⁸F]9 for evaluating target occupancy in vivo in higher species. In conclusion, our results indicated that [¹⁸F]9 is a promising PDE10A PET radioligand for clinical translation.KEY WORDS: Phosphodiesterase 10A, PET radioligand, ¹⁸F, Spirocyclic iodonium ylide, Nonhuman primate, Target occupancy     

对黑布药膏两种传统制作工艺比较的研究

黑布药膏为首都医科大学附属北京中医医院皮肤科常用的醋制软膏制剂,被收入1984版北京市卫生局编制的《医疗单位制剂规程》中,由五倍子粉、蜈蚣面、冰片、蜂蜜、陈醋等制作而成。本药膏是由国内著名皮外科专家赵炳南教授研制,具有破瘀软坚散     

NBT光照法测定聚（2-乙基-2-NFDE6唑啉）化超氧化物歧化酶模拟物脂质体的活性

 目的 建立聚（2-乙基-2-NFDE6唑啉）[poly(2-ethyl-2-oxazoline),PEOZ]修饰超氧化物歧化酶（superoxide dismutase,SOD）模拟物脂质体的活性测定方法。方法 以薄膜分散法制备聚（2-乙基-2-NFDE6唑啉）化超氧化物歧化酶模拟物脂质体,利用氮蓝四唑（NBT）光照法对超氧化物歧化酶模拟物及聚（2-乙基-2-NFDE6唑啉）化超氧化物歧化酶模拟物脂质体的活性进行测定。结果 超氧化物歧化酶模拟物的抑制率曲线方程为IR%=33.421lnρ+49.715（r²=0.999 2）,IC₅₀为1.008 6×10^-3 μmol·L^-1;聚（2-乙基-2-NFDE6唑啉）化超氧化物歧化酶模拟物脂质体的抑制率曲线方程IR%=33.521lnρ+49.671（r²=0.999 1）,IC₅₀为1.009 9×10^-3 μmol·L^-1。结论 氮蓝四唑光照法操作简单、稳定可靠、经济实用,可用于超氧化物歧化酶模拟物聚（2-乙基-2-NFDE6唑啉）脂质体的活性测定;经脂质体包裹后超氧化物歧化酶模拟物的活性未发生变化。     

腺苷促进体外培养神经干细胞增殖作用研究

目的研究腺苷促进体外培养神经干细胞（NSCs）增殖作用。方法取新生小鼠大脑进行神经干细胞原代培养,观察神经球生成情况,特异性蛋白质免疫细胞化学染色和BrdU标记鉴定并判断其增殖能力;将腺苷按0.4,2.0,10.0 μmol•L 13个浓度加入神经干细胞培养基,同时设立溶媒对照组和阳性对照组,通过观察神经球形态、神经球生成数目及 MTT法定量比较,分析不同浓度腺苷对神经干细胞分裂增殖的影响。结果培养物中有大量神经球生成,神经干细胞特异性蛋白质免疫细胞化学染色呈阳性,BrdU标记亦呈阳性反应,所培养的细胞为神经干细胞,具有增殖能力;腺苷中、高浓度组神经球数目、MTT比色结果明显高于溶媒对照组。结论腺苷具有促进NSCs增殖作用。     

Protective effects of peony glycosides against corticosterone-induced cell death in PC12 cells through antioxidant action

Aim of the study

Previous studies in our laboratory have shown that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. However, the molecular mechanism by which TGP exerts antidepressant-like effect is not fully understood. This study examined the protective ffects of TGP against corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells and ts possible mechanisms.

Materials and methods

The direct antioxidant effect of TGP was investigated by using a 2,2′-azinobis-(3-ethylbenzothiazoline- 6-sulphonic acid) (ABTS) radical cation-scavenging assay in a cell-free system. PC12 cells were treated with 200 μM of corticosterone in the absence or presence of TGP in varying concentrations for 48 h. Cell viability, lactate dehydrogenase (LDH) activity, intracellular reactive oxygen species (ROS) level, malondialdehyde (MDA) content, glutathione (GSH) content, superoxide dismutase (SOD) activity, and catalase (CAT) activity were then determined.

Results

TGP displayed antioxidant properties in the cell-free system, and the IC50 value in the ABTS radical cation-scavenging assay was 9.9 mg/L. TGP treatment at increasing doses (1-10 mg/L) protected against corticosterone-induced cytotoxicity in PC12 cells in a dose-dependent manner. The cytoprotection afforded by TGP treatment was associated with decreases in the intracellular ROS and MDA levels, and increases in the GSH level, SOD activity, and CAT activity in corticosterone-treated PC12 cells.

Conclusion

The results suggest that TGP has a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action.     

Evaluation of the anti-proliferative properties of selected psoriasis-treating Chinese medicines on cultured HaCaT cells

Psoriasis is a chronic inflammatory skin disorder, which affects approximately 2-3% of the population worldwide. The current conventional therapy cannot offer satisfactory clinical results for most of the patients, largely due to the fact that many anti-psoriatic drugs have serious side effects and psoriasis is prone to developing drug resistance after long term exposure. Traditionally, Chinese herbal medicine has been extensively used to treat psoriasis and produced promising clinical results; however, its underlying mechanisms of action have not been systematically investigated. The aim of this study was to investigate those Chinese medicinal materials, which are commonly prescribed in Chinese medicine practice for psoriasis, for their anti-proliferative effects on HaCaT cells in vitro. Sixty Chinese medicinal materials were selected and extracted with 80% aqueous ethanol. The dry extracts were evaluated for their anti-proliferative activities by microplate SRB and MTT assays. Three Chinese medicinal materials i.e. the root of Rubia cordifolia L. (Rubiaceae), Realgar and the rhizome of Coptis chinensis Franch. (Ranunculaceae) were found to have significant anti-proliferative effects, with IC(50) being 1.4, 6.6 and 23.4 microg/ml, respectively as measured by MTT assay. While Realgar was also able to modestly inhibit the growth of Hs-68 cells in vitro, Rubia cordifolia and Coptis chinensis did not exert cytotoxicity to this human fibroblast cell line.     

基于数据分析的NFASC与胃癌预后的关系及相关机制

目的:探讨NFASC在胃癌中的预后意义及相关机制。方法:从人类肿瘤相关基因表达汇编（Gene Expression Omibus,GEO）数据库中下载GSE62254胃癌数据集,分析NFASC表达与胃癌临床病理学参数的相关性及对预后的影响;利用Cox模型分析影响胃癌患者总生存期的因素并建立预后预测列线图模型;采用基因集富集分析(GSEA)方法预测NFASC参与的信号通路。结果: NFASC高表达的胃癌患者总生存时间（overall survival,OS）更短（P<0.05）,NFASC表达与患者年龄、T分期及Lauren分型相关（P均<0.05）。NFASC高表达富集了TGF-β信号通路、mTOR信号通路、MAPK信号通路和Wnt信号通路等与肿瘤细胞增殖密切相关的通路（P<0.05,FDR<0.25）。结论: NFASC是胃癌的不良预后因素,其表达可能成为胃癌预后预测生物标志物。