Synthesis and in vivo distribution of 2-deoxy-2-aminodiglucose-prednisolone conjugate(DPC)

In order to develop a novel kidney-targeted drug delivery system,a small molecular carrier（2-deoxy-2-aminodiglucose） was synthesized,and then the 2-deoxy-2-aminodiglucose-prednisolone conjugate（DPC） was synthesized to verify the kidney targeting capability of the carrier.Both 2-deoxy-2-aminodiglucose and DPC were confirmed by NMR and MS spectrum.The tissue distribution studies showed that DPC presented an excellent kidney targeting property in vivo,compared with prednisolone group, 4.9-fold of drug concentration in kidney was observed in the DPC group.Thus,it indicated that 2-deoxy-2-aminodiglucose could be a potential carrier for kidney-targeted drug delivery.

Comparisons between glucose analogue 2-deoxy-2-(^(18)F)fluoro-D-glucose and ^(18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM: To compare 2-deoxy-2-(^(18)F)fluoro-D-glucose(^(18)FFDG) and ^(18)F-sodium(^(18)F-NaF) positron emission tomography/computed tomography(PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent ^(18)F-FDG and ^(18)F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity(Se), specificity(Sp), overall accuracy, positive and negative predictive values, error rate, and Youden's index. Mc Nemar's χ~2 test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the coregistered CT(sclerotic, lytic, mixed, no-lesions) and the divergent site of disease(skull, spine, ribs, extremities, pelvis). The impact of adding ^(18)F-Na F PET/CT to the work-up of patients was also measured in terms of change in their management due to ^(18)F-Na F PET/CT findings. RESULTS: The two imaging methods of ^(18)F-FDG and ^(18)F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively(Mc Nemar's χ~2 = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis(Mc Nemar's χ~2 = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, ^(18)F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis(P < 0.002) and vertebral localizations(P < 0.002); ^(18)F-Na F PET/CT was more accurate in detecting sclerotic(P < 0.005) and rib lesions(P < 0.04). ^(18)F-Na F PET/CT led to a change of management in 3 of the 45 patients(6.6%) by revealing findings that were not detected at ^(18)F-FDG PET/CT. CONCLUSION: ^(18)F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of ^(18)F-Na F PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of ^(18)F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings(i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative ^(18)F-FDG PET and conventional imaging).

Stereoselective Synthesis and Crystal Structure Analysis of N-Naphthyl-2-deoxy-α-D-ribopyranosylamine

A new compound N-naphthyl-2-deoxy-α-D-ribopyranosylamine was synthesized and structurally determined. It crystallizes in the orthorhombic system, space group P212121 with a = 8.361（2）, b = 12.432（3）, c = 12.791（4） A^°, Z= 4, V= 1329.6（6） A^°^3, Dc= 1.295 g/cm^3, F（000） = 552, Cl5H17NO3 and Mr= 259.30. All the active hydrogen atoms are involved in the formation of hydrogen bonds in the molecule.

Bioactivity‑Guided Isolation of Totarane‑Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3‑Deoxy‑2α‑hydroxynagilactone E

Bioactivity-guided phytochemical investigation of Podocarpus neriifolius D.Don.(Podocarpaceae)has led to the isolation of one new(2)and three known(1,3,and 4)B-type podolactones,along with three totarane-type diterpenes(5-7).Their structures were determined by interpretation of High Resolution ElectroSpray Ionization Mass Spectrometry(HRESIMS)and 1D and 2D NMR data,and comparison with the values reported in the literature.The structure of compound 1,previously identifed as 3-deoxy-2α-hydroxynagilactone E(8),was revised as its 2β-epimer,which has been reported recently as a new compound.All of the isolates were evaluated for their antiproliferative activity against a panel of four human cancer cell lines,namely,ovarian(OVCAR3),breast(MDA-MB-231),colon(HT-29),and melanoma(MDA-MB-435),and compounds 1 and 3 were found to be cytotoxic with IC_(50) values in the low micromolar range for most of the cell lines used.The major compound,inumakilactone A(3),was further tested in vivo using the HT-29,MDA-MB-435,and OVCAR3 cells in a murine hollow fber model,for the frst time.

Comparison of Positron Emission Tomography Using 2-[^18F]-fluoro-2-deoxy-D-glucose and 3-deoxy-3-[^18F]-fluorothymidine in Lung Cancer Imaging

Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography （CT） imaging results remains a significant challenge. The 2-[^18F]-fluoro-2-deoxy-D-glucose （^18F-FDG） positron emission tomography （PET）/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[^18F]-fluorothymidine （^18F-FLT） in lung cancer PET/CT imaging. Methods： The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established （n = 12）, and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values （SUVs）, and Ki-67 proliferation marker expression were investigated. Results： The cell-tracer binding ratio for the A549 cells using the ^18F-FDG was greater than the ratio using 18F-FLT （P 〈 0.05）. The Ki-67 expression showed a significant positive correlation with the ^18F-FLT binding ratio （r = 0.824, P〈 0.01）. The tumor-to-nontumor uptake ratio of ^18F-FDG imaging in xenografts was higher than that of ^18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of ^18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of ^18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of ^18F-FDG and ^18F-FLT （r = 0.658, P〈 0.05 and r = 0.724, P〈 0.01, respectively）. Conclusions： The ^18F-FDG uptake ratio is higher than that of ^18F-FLT in A549 cells at the cellular level.^18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.

15-deoxy-△12,14-prostaglandin J2 ameliorates endotoxin-induced acute lung injury in rats

Background A proinflammatory milieu emerging in the lung due to neutrophil accumulation and activation is a key in the pathogenesis of acute lung injury （ALI）.15-deoxy-△12,14-prostaglandin J2 （15d-PGJ2）,one of the terminal products of the cyclooxygenase-2 pathway,is known to be the endogenous ligand of peroxisome proliferator-activated receptor y （PPAR-y） with multiple physiological properties.Growing evidence indicates that 15d-PGJ2 has anti-inflammatory,antiproliferative,cytoprotective and pro-resolving effects.We investigated whether 15d-PGJ2 has a protective effect against endotoxin-induced acute lung injury in rats.Methods Twenty-four male Wistar rats were randomly assigned into four groups （n=6 per group）：sham＋vehicle group,sham＋15d-PGJ2 group,LPS＋vehicle group,and LPS＋15d-PGJ2 group.The rats were given either lipopolysaccharide （LPS,6 mg/kg intravenously） or saline,and pretreated with 15d-PGJ2 （0.3 mg/kg intravenously） or its vehicle （dimethyl sulphoxide） 30 minutes before LPS.Histological alterations,wet/dry weight （W/D） ratio and myeloperoxidase （MPO） activity as well as tumor necrosis factor （TNF）-α and cytokine-induced neutrophil chemoattractant-1 （CINC-1） levels were determined in lung tissues four hours after LPS injection.Immunohistochemical analysis for intercellular adhesion molecule-1 （ICAM-1） expression and Western blotting analysis for nuclear factor （NF）-κB p65 translocation and IκBα protein levels were also studied.Results 15d-PGJ2 pretreatment significantly attenuated LPS-induced lung injury,and reduced the increased W/D ratio,MPO activity,TNF-α,CINC-1 levels,and ICAM-1 expression in the lung.15d-PGJ2 also suppressed the nuclear NF-ΚB p65 translocation and increased cytosolic IKBα levels.Conclusions 15d-PGJ2 protects against endotoxin-induced acute lung injury,most likely through the reduction of proinflammatory protein levels during endotoxemia subsequent to the inhibition of NF-ΚB activation.

RNase A-catalyzed synthesis of dinucleotides containing 2' -deoxy-2' -fluoro-pyrimidinenucleosides at 3'-termini

RNase A catalyzes the hydrolysis of ribonucleic acids to form oligonucleotide fragments containing pyrimidineribonucleoside 2’, 3’-cyclic phosphate at the 3’-termini, which are then further hydrolyzed to produce oligonucleotide fragments with 3’ -phosphate group as the final products. This enzyme can also catalyze the formation of internucleotide linkage from pyrimidineribonucleoside 2’, 3’-cyclic phosphate and a nucleoside component with

正电子显像剂^(18)F-FDG TracerlabFX-FDG法的制备与质量控制

目的探讨TracerlabFX-FDG法18F-脱氧葡萄糖(18F-FDG)的制备和质量控制方法。分析影响18F-FDG合成效率的因素。方法应用美国GE公司的加速器PETtrace,通过18O(p,n)18F核反应生产18F负离子,通过亲核取代反应合成18F-FDG,并对制备的18F-FDG注射液进行质量控制。结果采用TracerlabFX-FDG法制备18F-FDG,产率较高,可达65%~70%,高效液相色谱(HPLC)法测定的放射化学纯度、化学纯度均大于99%。结论18F-FDG注射液完全满足临床正电子发射断层显像(PET/CT)的检查需要。

The Role of ¹⁸F-FDG PET/CT in Staging Breast Carcinoma in Hanoi Oncology Hospital, Vietnam

Purpose: This study aimed to evaluate the role of 18F-FDG PET/CT scans in staging breast carcinoma. Materials and Methods: A descriptive study on 46 patients who were diagnosed with breast carcinoma in Hanoi Oncology Hospital, Vietnam from June 2019 to June 2021. Those patients underwent 18F-FDG PET/CT scans for pre-treatment staging. Results: There was a positive correlation between the size of primary tumors and their SUV (p < 0.0001, r = 0.759). The mean SUV was reported to be 2.5 for tumors under 2 cm, 5.89 for tumors from 2 - 5 cm, 13.6 for tumors above 5 cm, and 8.23 for skin invasive lesions. In terms of regional lymph node metastasis detection, the sensitivity and specificity of 18F-FDG PET/CT were 75% and 100%, respectively. The rate of distant metastasis detection was 15.2% (7/46 patients). Metastatic lesions were found in bone, lungs, liver, and lymph nodes. There was a significant difference in SUV among organs (p < 0.001), with the highest SUV found in bone metastasis. The rates of stage I, II, III and IV diagnosed after PET/CT are 8.7%;45.7%;30.4% and 15.2% respectively, compared to 10.9%;54.3%;32.6%;2.2% before taking 18F-FDG PET/CT. After PET/CT, 17.4% patients (8/46) had their treatment plan changed. Conclusions: 18F-FDG PET/CT plays an important role in staging breast carcinoma. Determining accurately the breast carcinoma stage by 18F-FDG PET/CT could help alter treatment strategy to best suit with patients, and avoid unnecessary surgery.

百尾参化学成分的分离与鉴定

目的研究百尾参Disporum cantoniense的化学成分。方法利用各种色谱技术进行分离,运用现代光谱技术鉴定化合物结构。结果从百尾参中分离得到16个化合物,分别鉴定为马来酸酰亚胺-5-肟(1)、4-methylene-5-oxopyrrolidine-2-carboxylic acid(2)、胸腺嘧啶(3)、腺嘌呤核苷(4)、5′-deoxy-5′-methylamino-adenosine(5)、乙基-α-L-鼠李糖(6)、岩白菜素(7)、4-羟基-2-甲氧基苯基-6-脱氧-α-L-吡喃木糖苷(8)、(-)-表儿茶素(9)、(6R,9R)-roseoside(10)、3-(4-羟基-3,5-二甲氧基苯基)-丙烷-1,2-二醇(11)、3-羟基-5-(p-羟基苯基)-戊酸(12)、1-核糖醇基-2,3-二酮-1,2,3,4-四氢-6,7-二甲基-喹喔啉(13)、(6S,9R)-vomifoliol(14)、3,4-二羟基苯酰甲醇(15)和1,2-二羟基-1-(4-羟基-3,5-二甲基苯基)-乙烷(16)。结论化合物1、2、5~9、12~16为首次从该属植物中分离得到;化合物1、2、5~10、12~16为首次从该植物中分离得到。

披针叶茴香果实的化学成分研究

目的研究八角科（Illiciaceae）植物披针叶茴香（Illicium lanceolatum）果实的化学成分。方法应用硅胶、Sephadex LH-20、MCI等各种色谱技术进行分离纯化，根据化合物的理化常数和波谱数据鉴定其结构。结果从披针叶茴香果实的体积分数95％乙醇提取物中分离得到12个化合物，通过渡谱数据和理化常数分别鉴定为2，4-dihydroxy—allylbenzene-2-O-β-D—glucopyranoside（1），（＋）-儿茶素（2），槲皮素-3-O-β-L-鼠李糖苷（3），芦丁（4），异鼠李素-3-D-β-D-芸香糖苷（5），6-deoxy-1-hy—droxy neoanisatin（6），莽草毒素（7），icarisideE3（8），（75，8R）-urolignoside（9），对羟基苯甲酸（10），莽草酸（11），β-谷甾醇（12）。结论化合物1，4～6，8～10为首次从该植物中分离得到。

Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer＇s Disease-related Biomarker in 5XFAD Mice

Background：Early diagnosis assumes a vital role in an effective treatment of Alzheimer＇s disease （AD）.Most of the current studies can only make anAD diagnosis after the manifestation of typical clinical symptoms.The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.Methods：A total of 14 5XFAD mice （at 3 and 6 months old）,with 14 age-matched wild-type （WT） mice as control,were enrolled in this case-control study.Morris water maze test was performed to evaluate the cognitive function;buried food pellet test and olfactory maze test were employed to investigate the olfactory function;immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-（18F） fluoro-D-glucose （[18F]-FDG） uptake in the hippocampus and cerebral cortex.Results：With the increasing age,cognitive performance （P =0.0262） and olfactory function were significantly deteriorated （day 1 P =0.0012,day 2 P =0.0031,day 3 P =0.0160,respectively） and the （18F）-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb （P 〈 0.0001）,hippocampus （P =0.0121）,and cerebral cortex （P 〈 0.0001）.Of note,in 3-month-old 5XFAD mice,a significant decline of （18F）-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice （P =0.023） while no significant difference was present when the uptakes in other cerebral regions were compared.Conclusions：The decline of （18F）-FDG uptake in the olfactory bulb occurs earlier than other incidents,serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.