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A series of novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored in this report with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl 4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 μM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.

Alkaloids are important chemical components in tobacco. In order to understand the genetic architecture of alkaloids in tobacco and identify major effect loci controlling alkaloids related traits, QTL mapping on tobacco alkaloids was performed. A set of 271 recombinant inbred lines (RIL) were constructed with Y3 and K326 as the parents. The RIL population was planted in Yanhe, Yuxi, Yunnan province and Shilin, Kunming, Yunnan province in 2018, 2019, and 2020, respectively. Five alkaloid phenotypes including total plant alkali (TPA), nicotine (NIC), nornicotine (NOR), anabasine (ANAB), and anatabine (ANAT) were measured. A linkage map of 46,129 markers was constructed by genome sequencing of the population. QTL mapping was performed by the software QTLNetwork 2.0 which was developed based on the mixed linear model. A total of 15 QTLs with significant additive effects were identified. The contribution rate of additive effect to the corresponding phenotypes varied from 0.58% to 11.57%. Four major QTLs, qTPA14 for total plant alkali, qNIC14 for nicotine, qANAB14 for anabasine, and qANAT14 for anatabine, accounted for more than 10% of phenotypic variation of the corresponding traits, which were located in linkage group 14. Six QTLs with significant additive-by-environment interaction effects were detected, their additive-by-environment interaction effects explained the phenotypic variation of 0.80%--1.81%. Five pairs of QTLs with significant additive-by-additive epistasis effects were detected, accounting for phenotypic variation from 0.15% to 2.31%, while two pairs of QTLs were detected with significant epistasis-by-environment interaction effects, which explaining the proportion of phenotypic variation from 0.81% to 1.16%. The results pave a foundation for further isolation of candidate genes, the dissection of genetic mechanism, and the molecular improvement of tobacco alkaloid traits. [ABSTRACT FROM AUTHOR]

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db−/− mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db−/− control, db/db−/− 50 mg, db/db−/− 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db−/− mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db−/− mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db−/− mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db−/− group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db−/− mice (P < 0.05). NF-κB levels were obviously higher in the db/db−/− group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db−/− mice (P < 0.05). There was a trend of increased autophagosomes in db/db−/− mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db−/− mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db−/− mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical manifestations and pathological characteristics of pulmonary papillary adenocarcinoma with psammoma bodies metastasis to right frontal lobe of brain. Methods The clinical manifestations, pathological features and differential diagnosis were studied in one case of pulmonary papillary adenocarcinoma with psammoma bodies metastasis to right frontal lobe. Related literatures were also reviewed. Results A 56-year-old male suffered from intermittent headache for 3 years in fronto - occipital region without significant incentives. Cranial MRI examination revealed a space-occupying lesion in right frontal lobe, which was considered as meningioma. In operation, the tumor located in the right frontal lobe was tough and red-grey in color, with clear boundary and abundant blood supply. Histopathological examination revealed the tumor was arranged in papillary pattern. The tumor cells were large, with eosinophilic cytoplasm, round or oval nuclei and small red nucleoli. Especially, a plenty of psammoma bodies were found in tumor tissue and mesenchymal tissue. Immunohistochemical staining found that the tumor cells were positively expressed for cytokeratin (CK), epithelial membrane antigen (EMA), CK19, thyroid transcription factor- 1 (TTF - 1) and Napsin A, and showed focal positive expression of P53. Ki-67 labeling index was 5%-10%. The tumor cells were negative for glial fibrillary acidic protein (GFAP), S-100 protein (S-100), thyroglobulin (TG), Galectin-3 protein, progestrone receptor (PR) and vimentin (Vim). Combined with the results of chest 1SF-FDG-PET CT, the final diagnosis was pulmonary papillary adenocarcinoma with psammoma bodies metastasis to right frontal lobe. The patient underwent auxiliary radiotherapy and chemotherapy after operation. The patient was followed for 12 months and no recurrence was seen. Conclusions This case is very rare. Understanding the patient's history and differentiating from other primary intracalvarium tumors is one of the key steps to give the right pathological diagnosis and clinical therapy. In order to avoid misdiagnosis, the diagnosis needs to be differentiated from other primary intracalvarium tumors, including papillary meningioma, papillary tumor of choroid plexus, papillary ependymoma, papillary glioneuronal tumors as well as metastatic papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]