An investigation into the mechanism of nobiletin's inhibition of papillary thyroid cancer using network pharmacology analysis and experimental pharmacology.

OBJECTIVE: Surgery and radioactive iodine therapy are the main treatments for papillary thyroid carcinoma (PTC), and effective drugs are lacking. As a promising natural product, nobiletin (NOB) has a wealth of pharmacological activities like anti-tumor, antivirus, and other effects. In this research, bioinformatics methods and cellular assays were combined to explore how NOB inhibited PTC. MATERIALS AND METHODS: Our NOB targets were derived from three databases, including the SwissTargetPrediction database, Traditional Chinese Medicine System Pharmacology Database, and the TargetNet server. Four databases were used to identify disease-related targets: GeneCards, PharmGkb, Online Mendelian Inheritance in Man, and DisGeNET. Finally, cross-targets of disease and drug were deemed as pharmacological targets, and they were used for GO and KEGG enrichment analysis. STRING and Cytoscape were applied for PPI Network and core Targets Ranking. Molecular docking analysis validated binding affinity values for NOB and core targets. By using cell proliferation and migration assays, NOB was assessed for its effects on PTC proliferation and migration phenotype. Western blot validated the downregulation of the PI3K/Akt pathway. RESULTS: (1) Preliminarily, 85 NOB targets were predicted for NOB intervention in PTC. (2) Our core target screening identified TNF, TP53, and EGFR, and our molecular docking results confirmed good binding between NOB and protein receptors. (3) NOB inhibited proliferation and migration of PTC cells. PI3K/AKT pathway target proteins were downregulated. CONCLUSIONS: (1) Bioinformatics analyses revealed that NOB may inhibit PTC by regulating TNF, TP53, EGFR and PI3K/AKT signalling pathway. (2) As evidenced by cell experiments, there was an inhibition of proliferating and migrating PTCs by NOB via the PI3K/AKT signalling pathway.

Epigallocatechin-3-gallate local pre-exposure application prevents SHIV rectal infection of macaques.

Epigallocatechin-3-gallate (EGCG), a natural and major ingredient of green tea, has been shown to have anti-inflammation and anti-HIV-1 properties. We demonstrated that the intrarectal administration of EGCG could protect rhesus macaques from repetitive, intrarectal challenges with low-dose SHIVSF162P3N. This protection has a per-exposure risk reduction of 91.5% (P = 0.0009; log-rank test) and a complete protection of 87.5% (P < 0.001; Fisher's exact test). All protected animals showed no evidence of systemic and mucosal SHIV infection as demonstrated by the absence of viral RNA, DNA and antibodies. In contrast, all controls became infected after repeated SHIV challenges (a median of 2.5 times, range of 1-8 times). Mechanistically, EGCG could block the binding of HIV-1 gp120 to CD4 receptor and suppress the macrophage infiltration/activation in the rectal mucosa of macaques. These data support further clinical evaluation and development of EGCG as a novel, safe and cost-effective microbicide for preventing sexual transmission of HIV-1.

Effects of isolation housing and timing of drug administration on amikacin kinetics in mice.

AIM: To study the influences of social condition and drug administration time on amikacin metabolism in mice. METHODS: Forty Male ICR mice were randomly assigned into 4 groups according to 1) housing condition: individual housing (I, one mouse in a cage) or aggregated housing (A, 10 mice in a cage) and 2) drug administration time: at midday (D) or at midnight (N), i.e. I-D, I-N, A-D, and A-N groups. Amikacin was injected s.c. 15 mg.kg-1 after 4 wk of raising at D or N. Blood samples were taken at 5, 10, 15, 20, 30, and 60 min after medication in each mouse. Plasma amikacin was measured by enzyme immunoassay. The concentration-time data were fitted with one-compartment open model in each mouse and data were analyzed with group t test. RESULTS: The clearance (Cl) of amikacin was larger and the half-life (T1/2) was shorter in A-N group than in A-D or I-N groups respectively. AUC(0-1) in A-N group was less than in I-N group. No differences of kinetic parameters between 2 isolated housing (I-D and I-N) groups were found. CONCLUSION: Aggregated housing and midnight drug administration increased the disposition of amikacin.

[Macrological identification of original and commercial Chinese drug gusuibu (Rhizoma drynariae)].

Twelve original species and 7 commercial species of Chinese drug Gusuibu were identified and discussed based on macrological observation and comparison. The survey of 65 samples collected from 23 provinces throughout the country showed that at the present time the major species of commercial Gusuibu is derived from the rhizomes of Drynaria fortunei, which makes up more than 70 percent of the total samples.

Isolation of (-)-gossypol from natural plant.

(-)-Gossypol has been isolated from cottonseed of G. barbadense L. Three Gossypium species were studied for the isolation. The study has also revealed a correlation between the optical activity of gossypol isolated and the species of cottonseed used. Gossypol isolated from the species G. barbadense is always found to be levorotatory caused by an excess of (-)-gossypol, whereas that from the species G. hirsutum is always dextrorotatory caused by an excess of (+)-gossypol. Results of most samples (cultivars) showed that optical purity of gossypol isolated from G. barbadense varied from 10-25%, while that from G. hirsutum varied from 10-20%. This is the first report of (-)-gossypol occurring naturally.

PIP: Both (+ and -)-gossypol and (+)-gossypol have been found to be naturally occurring, while no plant producing (-)-gossypol has to date been located. This study isolated (-)-gossypol from the cottonseed of Gossypium barbadense L. Cottonseed from G hirsutum L and G arboreum L was also investigated. The (-)-gossypol content was consistently higher than the (+) gossypol content for all 16 sample of G barbadense studied, while the (+)-gossypol content was higher in the 10 G hirsutum L samples and the 1 G arboreum L sample. The rotation property of gossypol was mainly correlated with the species of the cottonseed; the area where the cottonseed was cultivated had no effect. Gossypol isolated from G barbadense was always levorotatory as a result of the excess of (-)-gossypol, whereas that from the other 2 species studied was always dextrorotatory due to the excess of (+)-gossypol. The optical purity of gossypol isolated from G barbadense ranged from 10-25%, and that from G hirsutum varied from 10-20%.

Endemic selenium intoxication of humans in China.

An endemic disease was discovered in 1961 in parts of the population of Enshi County, Hubei Province of the People's Republic of China. During the years of the highest prevalence, from 1961 to 1964, the morbidity was almost 50% in the 248 inhabitants of the five most heavily affected villages; its cause was determined to be selenium intoxication. The most common sign of the poisoning was loss of hair and nails. In areas of high incidence, lesions of the skin, nervous system, and possibly teeth may have been involved. A case is reported of a middle-aged, female hemiplegic, whose illness and death apparently were related to selenosis. Daily dietary intakes of selenium, estimated after the peak prevalence had subsided, averaged 4.99 (range 3.20 to 6.69) mg and hair and blood selenium levels averaged 32.2 and 3.2 micrograms/ml, respectively. Up to 1000x differences occurred when selenium contents of vegetables, cereals, scalp hair, blood, and urine from the selenosis areas were compared with those from Keshan disease (selenium deficiency) areas. The ultimate environmental source of selenium was a stony coal of very high selenium content (average more than 300 micrograms/g; one sample exceeded 80,000 micrograms/g). Selenium from the coal entered the soil by weathering and was available for uptake by crops because of the traditional use of lime as fertilizer in that region. This particular outbreak of human selenosis was due to a drought that caused failure of the rice crop, forcing the villagers to eat more high-selenium vegetables and maize and fewer protein foods.