The risks of artificial intelligence: A narrative review and ethical reflection from an Oral Medicine group.

As a relatively new tool, the use of artificial intelligence (AI) in medicine and dentistry has the potential to significantly transform the healthcare sector. AI has already demonstrated efficacy in medical diagnosis across several specialties, used successfully to detect breast, lung and skin cancer. In Oral Medicine, AI may be applied in a similar fashion, used in the detection and diagnosis of oral cancers and oral potentially malignant diseases. Despite its promise as a transformative diagnostic aid, the use of AI in healthcare presents significant safety, reliability and ethical concerns. There is no formal consensus on the safe and ethical implementation of AI systems in healthcare settings, but the literature converges on several key principles of ethical AI use including transparency, justice and fairness, non-maleficence, responsibility and privacy. This article provides a narrative review of the key ethical issues surrounding AI use in medicine, and reflects on these, providing view-points of a bioethicist and Oral Medicine clinicians from several units.

Twelve novel sesquiterpenes with anti-inflammatory and cholesterol-lowering activities from burdock leaves.

Nine new cadinane-type sesquiterpenoids (1-9) and three new eucalyptane -type sesquiterpenes (10-12) were isolated from the ethyl acetate extract of Burdock leaves, which were commonly used for preventing or treating atherosclerosis in China. Their structures were confirmed by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis and ECD calculations. Compound 1 possessed the rare large conjugated skeleton. All the isolates were evaluated for anti-inflammatory and cholesterol-lowering activities by the LPS- and oxidized-low-density-lipoprotein-stimulated RAW 264.7 cells, respectively. As the results, all isolates could decrease the productions of NO, and down-regulate the accumulation of cholesterol. Among them, 4 showed the most potent cholesterol-lowering effect. For the high content of 4 in the herb, mechanistic study of 4 was performed and the results showed that 4 markedly reduced the release of pro-inflammatory mediators which was probably associated with inhibition of the PI3K/Akt and 5-LOX signaling pathways. The findings of this study demonstrated the anti-inflammatory/cholesterol-lowering effects of the new sesquiterpenes from burdock leaves, which provides chemical basis and scientific evidence for the herb used as anti-atherosclerosis agents for the further study. The sesquiterpene lactones of burdock leaves are expected to become new small molecule inhibitors for the treatment of AS.

[Iridoids of wine-processed Corni Fructus].

A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7ß-O-(2″-formylfuran-5″-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7ß-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7ß-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).

Four New Gallate Derivatives from Wine-Processed Corni Fructus and Their Anti-Inflammatory Activities.

Four new gallate derivatives-ornusgallate A, ent-cornusgallate A, cornusgallate B and C (1a, 1b, 2, 3)-were isolated from the wine-processed fruit of Cornus officinalis. Among them, 1a and 1b are new natural compounds with novel skeletons. Their chemical structures were elucidated by comprehensive spectroscopy methods including NMR, IR, HRESIMS, UV, ECD spectra and single-crystal X-ray diffraction analysis. The in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. As the result, all compounds exhibited anti-inflammatory activities at attested concentrations. Among the tested compounds, compound 2 exhibited the strongest anti- inflammatory activity.

[Discovery and activity verification of reniformin A as an anti-tumor leading compound].

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.

Two new triterpenes from the roots of Pfaffia glomerata.

Pfaffia paniculata is a commercialized dietary supplement used as the substitute for the Asian ginseng in Brazil. We conducted the systematic isolation of the EtOAc fraction with anti-inflammatory effect and two new triterpenoids, along with 26 known compounds were characterized by means of MS and NMR analysis. Interestingly, the new compound 1 is the first seco-ring triterpenoid reported in the Pfaffia genus. Furthermore, among the known compounds, 14 and 15 exhibited anti-inflammatory activity in Caco-2 cells, but two new compounds showed no anti-inflammatory.

A new sesquiterpene lactone glycoside and a new quinic acid methyl ester from Patrinia villosa.

A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature.

Isolation and identification of antioxidant constituents from the flowers of Salvia miltiorrhiza.

A new salvianolic acid derivative, (7'E)-(7S, 8S)-salvianolic acid V (1), together with four previously described compounds (2-5) were obtained from the n-butanol fraction of Salvia miltiorrhiza flowers. Their structures were established by a series of spectroscopic methods, and the absolute configuration of 1 was determined by electronic circular dichroism (ECD) calculation. Salvianolic acids (1) and phenolic acids (2-4) showed stronger DPPH free radical scavenging abilities and certain protective effects against H2O2-induced human skin fibroblast (HSF) cells oxidative damage, in which compound 1 (IC50 7.12 µM) possessed more noticeable free radical scavenging activity than the positive control vitamin C (IC50 14.98 µM).

Anti-inflammatory diterpenoid alkaloids from Aconitum tanguticum (Maxim.) Stapf.

Fifteen undescribed diterpenoid alkaloids and seven known analogs were coisolated from the whole plant Aconitum tanguticum (Maxim.) Stapf. Their structures were elucidated based on spectroscopic methods. Among them, tangirine A was a heteratisine-hetidine-type bis-diterpenoid alkaloid, tanguticinines A-F were six hetidine-hetisine-type bis-diterpenoid alkaloids, tanguticinine G was one hetidine-atisine-type bis-diterpenoid alkaloid, and N-oxide anthoroidine B, 5-deoxyanthoridine B and N-oxide 5-deoxyanthoroidine B were three unusual hetidine-rearranged hetisine-type bis-diterpenoid alkaloids. In the bioassay, thirteen compounds showed some inhibitory effects on the secretion of NO and TNF-α in LPS-treated RAW 264.7 cells, with IC50 values of 67.56 µM-683.436 µM.

Sesquiterpene Lactams and Lactones With Antioxidant Potentials From Atractylodes macrocephala Discovered by Molecular Networking Strategy.

Atractylodes macrocephala rhizome (called Bái-zhú in China) has a long history as a functional food and herbal medicine in East Asia, especially China. Sesquiterpenoids are one of the main active compounds of Atractylodes macrocephala rhizome. This study aimed to explore the unknown sesquiterpenoids of A. macrocephala rhizome using a molecular networking strategy. Two new nitrogen-containing sesquiterpenoids, atractylenolactam A (1) and atractylenolactam B (2), and 2 new sesquiterpene lactones, 8-methoxy-atractylenolide V (6) and 15-acetoxyl atractylenolide III (7), along with 12 known analogs (3-5 and 8-16) were discovered and isolated. All the structures were assigned based on detailed spectroscopic analyses. The absolute configurations of 1, 2, 6, and 7 were established by time-dependent density functional theory ECD (TDDFT-ECD) calculations. All these compounds had different degrees of concentration-dependent activating effects on nuclear-factor-E2-related factor-2 (Nrf2).

A new ent-kaurane diterpene from Isodon henryi.

One new ent-Kaurane diterpenoid (1) was isolated from the ethyl acetate fraction of Isodon henryi. Along with ten diterpenoids (2-11) were isolated from this plant for the first time, including six 7,20-epoxy diterpenoids, three enmenol-type diterpenoids and one 6,7-seco-ent-kaurene diterpenoid. Their structures were elucidated by 1 D and 2 D NMR, confirmed by HRESIMS and electronic circular dichroism analyses. Furthermore, the cytotoxicities of twelve compounds were investigated in five human cancer cell lines, including A2780, BGC-823, HCT-116, HepG2 and HeLa. And the IC50 values of these diterpenoids ranged from 2.1 to 88.8 µM in the tested cell lines. Based on the molecular structures of 12 compounds and the bioassay results, it suggests that α,ß-unsaturated pentanone is the cytotoxic active site of 7,20 epoxy ent-kaurane diterpenoid, but it does not contribute much to enmenol-type diterpenoid.Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1675067.

Neuroinflammatory inhibitors from Gardneria nutans Siebold & Zuccarini.

Two new monoterpene indole alkaloid glycosides nutanoside A-B (1-2), two new phenolic glycoside esters nutanester A-B (6-7), together with five known compounds (3-5, 8-9) were isolated from the ethanol extract of Gardneria nutans Siebold & Zuccarini. Their structures were established on the basis of extensive spectroscopic analysis and TDDFT/ECD calculations. Compounds 1 and 2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids. Compounds 3, 4 and 6 displayed significant inhibitory effects on NO production in over-activated BV2 microglial cells, with the IC50 values of 2.29, 6.36, and 8.78 µM, respectively. Compounds 1, 5, 7 could significantly inhibit the mRNA expression of inflammatory factors TNF-α and IL-6 induced by LPS in BV2 microglial cells at the effective concentration. Moreover, compound 3 exhibited stronger cytotoxicities against U87 and HCT116 cell lines than taxol with IC50 values of 10.58 and 14.60 µM, respectively.

Correction: Neuroinflammatory inhibitors from Gardneria nutans Siebold & Zuccarini.

[This corrects the article DOI: 10.1039/D1RA05204G.].

Isolation and identification of two pairs of cytotoxic diterpene tautomers and their tautomerization mechanisms.

Discovering anticancer drugs that do not have adverse side effects has been a developing research field worldwide in recent decades. In this work, four previously undescribed cytotoxic diterpenoids were isolated from the aerial parts of Isodon excisoides. Interestingly, these four diterpenoids were two pairs of tautomers that were first reported in plants. Their structures were further elucidated using various spectroscopic methods. The tautomerization phenomenon and mechanism for these two pairs of tautomers were emphatically described. The theoretical simulation results indicated that the diterpene tautomerization is greatly related to certain factors, including the existence of a transition state, the change of bond length and the level of conversion energy; the tautomerization for the two pairs of tautomers is mainly caused by proton transfer. For bioassays, the cytotoxicities of the tautomers against five human cancer cell lines were also investigated. The results indicated that each of the four diterpenoids showed significant cytotoxicity in at least three cell lines and could serve as potential anticancer agents for further investigation.

Author Correction: Isolation and identification of two pairs of cytotoxic diterpene tautomers and their tautomerization mechanisms.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Isolation and identification of two new compounds from the Penicillium sp. SYPF7381.

Two new compounds, (7R, 2E, 5E)-3,5,7-trimethyl-2,5-octadienedioic-8-methyl ester (1) and neovasipyridone G (3), together with a new natural product compound (7R,2E,5E)-3,5,7-trimethyl-2,5-octadienedioic acid (2), and six known compounds (4-9) were isolated from Penicillium sp. SYPF7381. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 2 were determined by optical rotation. The absolute configuration of compound 3 was determined by means of electronic circular dichroism (ECD) calculation. In addition, the in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. Furthermore, the structure-antiinflammation activity relationships for these isolated compounds were summarized based on the experimental as well as the docking results.

(±) Benzomalvins E isolated from Penicillium sp. SYPF 8411 in the rhizosphere soil of Codonopsis clematidea.

(+) Benzomalvins E (1) and (-) Benzomalvins E (2), a pair of epimeric derivatives, together with three known benzomalvins (3-5), were isolated from solid cultures of a interrhizospheric fungus Penicillium sp. SYPF 8411. The planar structure of (+) Benzomalvins E (1) has been previously reported. While, the absolute configuration of compound 1 was established by X-ray crystallographic analysis for the first time. The planar structure of the new compound 2 were elucidated by detailed interpretation of their HR ESI-TOF MS and NMR spectroscopic data. The absolute configuration of compound 2 was established by Rh2(OCOCF3)4-induced CD spectral data and the electronic circular dichroic (ECD) method. Furthermore, the epimerization induced by pH, temperature and H2O was revealed. Benzomalvins (1-3, 5), a type of indoximod, enhanced the cytotoxic capability of 5-fluorouracil against A549.

Isolation and identification of two new compounds from the twigs and leaves of Cephalotaxus fortunei.

Two new compounds, namely 5-hydroxy-7-methoxy-6-methylchromone (1), and sesquiterpene X (6), together with 21 known compounds were isolated from the twigs and leaves of Cephalotaxus fortunei Hook. f. The structures of 1-23 were elucidated on the basis of spectroscopic analysis (1D/2D NMR, HR-ESI-MS and IR) and comparison with literature. The absolute configuration of compound 6 was determined by means of electronic circular dichroism calculation. The in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing lipopolysaccharide-induced nitric oxide production. Compounds 1 and 6 exhibited weak effects with percentage inhibitions of 24% and 35.60%, respectively. In addition, compounds 4, 9, and 14 have the potential to be developed as therapeutic agents for inflammatory diseases because of their significant anti-inflammatory activities and high content in C. fortunei.

Four new hybrid polyketide-terpenoid metabolites from the Penicillium sp. SYPF7381 in the rhizosphere soil of Pulsatilla chinensis.

A search for cytotoxic agents from cultures of the Penicillium sp., isolated from the rhizosphere soil of Pulsatilla chinensis, led to the isolation of four new hybrid polyketide-terpenoid metabolites (1-4), together with fourteen known compounds (5-18). Using a bioassay-guided fractionation approach, eighteen compounds were obtained from the ethyl acetate extract of this fungus. Structure elucidation was achieved by extensive analysis of spectroscopic data (1D/2D NMR, HRESIMS and IR). The absolute configurations of compounds 1-4 were determined by means of electronic circular dichroism (ECD) calculation. Compounds 1-4, 7-9, 11, 12, 14 and 17 were tested for their cytotoxicity against HL-60, THP-1 and Caco2 cell lines. Compound 1 showed potent cytotoxic capability against HL-60, THP-1 and Caco2 cell with IC50 values of 3.4µM, 4.3µM, 10.5µM, and compound 2 showed significant inhibiting activities against HL-60 cell line and THP-1 cell line (IC50=7.9µM, 11.3µM, respectively), using 5-fluorouracil as the positive drug with IC50 values of 6.4µM, 4.4µM, 56.6µM for HL-60, THP-1 and Caco2 cells, respectively. And compound 1 showed antibacterial activity toward Bacillus cereus (IC50=49µg/mL, IC90=111µg/mL) and Bacillus subtilis (IC50=10µg/mL, IC90=85µg/mL).