The selective sponging of miRNAs by OIP5-AS1 regulates metabolic reprogramming of pyruvate in adenoma-carcinoma transition of human colorectal cancer.

RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.

Hosimosines A-E, structurally diverse cytisine derivatives from the seeds of Ormosia hosiei Hemsl. et Wils.

Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O. hosiei have been used as traditional Chinese medicine to treat hernia, abdominal pain, blood stasis and amenorrhea. Cytisine-like and angustifoline type alkaloids were main components identified from this plant. In our research on the bioactive alkaloids from the promising Chinese medicinal plants, four new angustifoline type alkaloids (1-4) and a new cytisine-like alkaloid (5), named hosimosine A-E, together with 13 known analogues (6-18) were isolated from the seeds of O. hosiei. Their structures were elucidated by the extensive spectroscopic methods, especially the interpretation of NMR spectra and specific rotations, along with the methods of NMR and ECD calculation. Compounds 1-4 were identified as two pairs of epimers, whose relative configurations were deduced from density functional theory (DFT) calculations of NMR chemical shifts and DP4+ analysis, and absolute configurations were determined by comparison of their experimental and theoretical ECD spectra. Compound 5 displayed two sets of NMR data caused by the existence of tautomeric forms. Compounds 14, 17 and 18 were determined to be enantiomers of literature compounds. Some of the isolates exhibited moderate cytotoxic effects against HepG2, A2780 and MCF-7 cells.

Human brucellosis and fever of unknown origin.

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

Rearranged Diels-Alder Adducts and Prenylated Flavonoids as Potential PTP1B Inhibitors from Morus nigra.

Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 µM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 µM).

[Estimation of effects of liuwei Dihuang Wan on anti-inflammation in rat by HPLC-UV based metabonomic method].

OBJECTIVE: To understand the possibility of estimating the anti-inflammation effect of Liuwei Dihuang Wan (LWW) in rat by having developed HPLC-UV metabonomic technology. METHOD: The hydrophilic or lipophilic constituent group of LWW was extracted by distilled water or acetic ether respectively. The anti-inflammation effects of different LWW dosages and extractions were measured by traditional method respectively. Then, metabonomic analysis was performed. RESULT: The high dosage of LWW extraction (16.5 g x kg(-1))could inhibit the swell of rat palm significantly, but there are not statistically significant effect of low dosage group. Nevertheless, the metabonomic study showed that LWW extraction could restore obviously the rat HPLC-UV urinary profiling disturbed by inflammation in low dosage, especially the hydrophilic constituent group. CONCLUSION: Our study indicated that the developed metabonomic technology based on HPLC-UV might be used as a potentially powerful tool for estimating the anti-inflammation effect of LWW with sensitivity and integrity.

[Determination and pharmacokinetics of photosensitizer ZnPcS2P2 uptaken by K562 cells].

The di-sulfonated di-phthalimidomethyl phthalocyanine zinc (ZnPcS2P2) was an amphiphilic photosensitizer for photodynamic therapy of cancer. According to fluorescence analytical method, extracting efficiencies of 2.0% SDS (Wt%), 1.5% Triton X-100 (phi) and DMF for ZnPcS2P2 in K562 cells were compared. The results showed that 1.5% Triton X-100 was the most efficient reagent for the first time extracting. Using 1.5% Triton X-100 as extracting reagent, the kinetic curves of cellular uptake of ZnPcS2P2 as well as LDL-ZnPcS2P2 complex by K562 cells were determined. Compared with ZnPcS2P2, the maximum cellular uptake of LDL-ZnPcS2P2 by K562 was doubled, which indicated that LDL was an effective targeting delivery vehicle for ZnPcS2P2.