[Clinical Analysis of Epstein-Barr Virus Infection after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To analyze the risk factors of Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its impact on survival. METHODS: The clinical data of 347 patients who underwent their first allo-HSCT in our hospital from January 2014 to June 2021 were retrospectively analyzed. Patients were divided into EBV (n =114) and Non-EBV (n =233) groups according to whether they were infected with EBV. The incidence of EBV infection after allo-HSCT was calculated, and the risk factors of EBV infection were analyzed. RESULTS: A total of 114(32.8%) patients presented EBV infection (all peripheral blood EBV-DNA were positive). EBV infection occurred in 88 patients within 100 days after transplantation, which accounted for 77.2% of all patients with EBV infection. 5 cases (1.44%) were confirmed as post-transplant lymphoproliferative disorder (PTLD). The median onset time of patients was 57(7-486) days after transplantation. Multivariate analysis showed that the use of ATG/ATG-F, occurrence of CMV viremia, and grade III-IV aGVHD were risk factors for EBV infection. Furthermore, compared to BUCY, the use of intensified preconditioning regimens containing FA/CA was significantly increased the risk of EBV infection. CONCLUSION: EBV infection is a common complication after allo-HSCT. Intensified preconditioning regimens, use of ATG/ATG-F, CMV viremia and grade III to IV aGVHD increase the risk of EBV infection after allo-HSCT.

Novel NanoLuc substrates enable bright two-population bioluminescence imaging in animals.

Sensitive detection of two biological events in vivo has long been a goal in bioluminescence imaging. Antares, a fusion of the luciferase NanoLuc to the orange fluorescent protein CyOFP, has emerged as a bright bioluminescent reporter with orthogonal substrate specificity to firefly luciferase (FLuc) and its derivatives such as AkaLuc. However, the brightness of Antares in mice is limited by the poor solubility and bioavailability of the NanoLuc substrate furimazine. Here, we report a new substrate, hydrofurimazine, whose enhanced aqueous solubility allows delivery of higher doses to mice. In the liver, Antares with hydrofurimazine exhibited similar brightness to AkaLuc with its substrate AkaLumine. Further chemical exploration generated a second substrate, fluorofurimazine, with even higher brightness in vivo. We used Antares with fluorofurimazine to track tumor size and AkaLuc with AkaLumine to visualize CAR-T cells within the same mice, demonstrating the ability to perform two-population imaging with these two luciferase systems.

Integrated Metabolomics and Proteomics Analysis Revealed Second Messenger System Disturbance in Hippocampus of Chronic Social Defeat Stress Rat.

Depression is a common and disabling mental disorder characterized by high disability and mortality, but its physiopathology remains unclear. In this study, we combined a non-targeted gas chromatography-mass spectrometry (GC-MS)-based metabolomic approach and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis to elucidate metabolite and protein alterations in the hippocampus of rat after chronic social defeat stress (CSDS), an extensively used animal model of depression. Ingenuity pathway analysis (IPA) was conducted to integrate underlying relationships among differentially expressed metabolites and proteins. Twenty-five significantly different expressed metabolites and 234 differentially expressed proteins were identified between CSDS and control groups. IPA canonical pathways and network analyses revealed that intracellular second messenger/signal transduction cascades were most significantly altered in the hippocampus of CSDS rats, including cyclic adenosine monophosphate (cAMP), phosphoinositol, tyrosine kinase, and arachidonic acid systems. These results provide a better understanding of biological mechanisms underlying depression, and may help identify potential targets for novel antidepressants.

Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD).

Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients.

Synthesis and antitumor activity of novel N-substituted carbazole imidazolium salt derivatives.

A series of novel N-substituted carbazole imidazolium salt derivatives has been prepared and investigated for their cytotoxic activity against five human tumor cell lines by MTS assay. The results indicated that the existence of 5,6-dimethyl-benzimidazole ring, substitution of the imidazolyl-3-position with a 2-bromobenzyl or naphthylacyl group, as well as alkyl chain length between carbazole and imidazole ring were important for the antitumor activity. Compound 61, bearing a 2-bromobenzyl substituent at position-3 of the 5,6-dimethyl-benzimidazole, showed powerful inhibitory activities and was more selective to HL-60, SMMC-7721, MCF-7 and SW480 cell lines with IC50 values 0.51-2.48 µM. Mechanism of action studies revealed that this new compound could remarkably induce cell cycle arrest and apoptosis in SMMC-7721 cells. This work provides alternative novel way for future drug development based on carbazole and imidazolium salt scaffolds.

Synthesis and antitumor activities of novel dibenzo[b,d]furan-imidazole hybrid compounds.

A series of novel hybrid compounds between dibenzo[b,d]furan and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of benzimidazole ring, and the substitution of the imidazolyl-3-position with a naphthylacyl or 4-methoxyphenacyl group, were vital for modulating cytotoxic activity. In particular, hybrid compound 60 was found to be the most potent derivatives against all of human tumor cell lines investigated, while compound 49 was found to be more selective against breast carcinoma (MCF-7) and myeloid liver carcinoma (SMMC-7721). Compound 60 can induce the G1 phase cell cycle arrest and apoptosis in SMMC-7721 cells.

Non-high-density lipoprotein cholesterol and other risk factors of mild cognitive impairment among Chinese type 2 diabetic patients.

OBJECTIVE: To identify some risk factors of MCI among patients with type 2 diabetes(T2DM) and to find if there is any correlation between these factors and the degree of cognitive decline. METHODS: A total of 155 patients with T2DM referred to the Department of Endocrinology at First Hospital of Qinhuangdao were enrolled. To assess MCI the Montreal Cognitive Assessment (MoCA) scoring system was used. There were 66 patients with MCI and 89 patients without MCI (control). HbAlc, blood lipid, liver and renal functions were measured in all subjects. RESULTS: Compared with the control group, type 2 diabetic patients with MCI had a longer duration of diabetes; higher non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, total cholesterol, HbA1c, and BMI; and lower high-density lipoprotein cholesterol (HDL-C) (P<0.05). The rates of patients with a history of habitual light-to-moderate alcohol consumption, a high proportion of Mediterranean-type diet, and regular physical activity were lower; and the rate of current smoking was higher in type 2 diabetic patients with MCI than the control group (P<0.05). Among patients with MCI, the results indicated that MoCA score was negatively correlated with non-HDL-C (r=-0.761 P<0.001). CONCLUSIONS: Our results suggest that non-HDL-C can act as a readily available method for estimating risk of MCI in Chinese type 2 diabetic patient in routine clinical practice. Good lifestyle likely reduces MCI risk in diabetic patients.

Design, synthesis and biological evaluation of novel hybrid compounds of imidazole scaffold-based 2-benzylbenzofuran as potent anticancer agents.

A series of novel hybrid compounds between 2-benzylbenzofuran and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or 4-methoxyphenacyl group were vital for modulating cytotoxic activity. In particular, hybrid compounds 46 and 47 were found to be the most potent derivatives against 5 strains human tumor cell lines and more active than cisplatin (DDP), and exhibited cytotoxic activities selectively against breast carcinoma (MCF-7) and myeloid liver carcinoma (SMMC-7721), respectively.

Application of T2 measurement on gradient echo T2-weighted imaging in differential diagnosis of intracranial hemorrhage and calcification.

BACKGROUND: Differential diagnosis of intracranial hemorrhage and calcification is a common problem encountered in clinical imaging diagnosis. The purpose of this study was to investigate the feasibility of T2 measurement on gradient echo (GRE) T2-weighted imaging (T2WI) in differential diagnosis of intracranial hemorrhage and calcification. METHODS: Thirty-eight hemorrhagic foci in 18 patients and 11 calcification foci in seven patients were included in this study. The diagnosis of hemorrhage and calcification was confirmed in all cases with enhanced T2 weighted angiography (ESWAN) magnetic resonance imaging (MRI) and CT respectively. The significance for the difference of T2 value between the central and peripheral areas of hemorrhage and calcification lesions was tested with univariate analysis of variance. RESULTS: The detection rate of GRE T2 WI on intracranial hemorrhage was 1.9-fold higher than that of CT, especially for the hemorrhage in the brainstem and cerebellum. However, GRE T2WI was far less sensitive to calcification than CT. There was a significant difference in the T2 value between the central area of hemorrhage and calcification (P < 0.001), though no difference in the T2 value was obtained between the peripheral area of hemorrhage and calcification (P > 0.05). CONCLUSIONS: Quantitative measurement of T2 value on GRE T2 WI with a single MRI examination provides a fast, convenient, and effective means in differential diagnosis between intracranial hemorrhage and calcification, which may thus reduce the medical cost and save precious time for clinical management.