Two novel cyclodepsipeptides containing an unusual anthranilic acid dimer and a d-phenyllactic acid residues, clavatustides A (1) and B (2), were identified from cultured mycelia and broth of Aspergillus clavatus C2WU isolated from Xenograpsus testudinatus, which lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. This is the first example of cyclopeptides containing an anthranilic acid dimer in natural products, and the first report of microbial secondary metabolites from the hydrothermal vent crab. Clavatustides A (1) and B (2) suppressed the proliferation of hepatocellular carcinoma (HCC) cell lines (HepG2, SMMC-7721 and Bel-7402) in a dose-dependent manner, and induced an accumulation of HepG2 cells in G1 phase and reduction of cells in S phase.

A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. testudinatus lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The known compound clavatustide B was also isolated and purified. This is the first example of a new hydrothermal vent microbial secondary metabolite produced in response to abiotic Zn treatment. The structures were established by spectroscopic means. The regulation of G1-S transition in hepatocellular carcinoma cell lines by clavatustide B was observed in our previous study. The purpose of the present study was to verify these results in other types of cancer cell lines and elucidate the possible molecular mechanism for the anti-cancer activities of clavatustide B. In different human cancer cell lines, including pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480), retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently suppressed cell proliferations in a dose-dependent manner. Although different cancer cell lines presented variety in Max effect dose and IC₅₀ dose, all cancer cell lines showed a lower Max effect dose and IC₅₀ dose compared with human fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases and a reduction in S phases (p < 0.05) were observed under clavatustide B treatment. The expression levels of 2622 genes including 39 cell cycle-associated genes in HepG2 cells were significantly altered by the treatment with 15 μg/mL clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator of clavatustide B-induced G1-S transition blocking in several cancer cell lines by using real-time PCR.

A 22-year-old patient suffering from both-side extreme hyperopia with amblyopia was corrected with an Artisan iris-fixated intraocular lens (IOL) implantation followed to clear lens extraction (CLE) with posterior chamber (PC)-IOL implantation. The preoperative refraction values were +17.75DS -1.50DC × 168° for the right eye and +17.25DS -0.75DC × 8° for the left eye. The uncorrected visual acuity (UCVA) was 20/200 bilaterally and the spectacle-corrected visual acuity (BSCVA) was 20/50 bilaterally. One year after Artisan iris-fixated IOL implantation, bilateral BSCVA was 20/50 with a refraction of +1.25DS -0.75DC × 13° for the right eye and +1.50DS -1.00DC × 55° for the left eye. The outcomes of an Artisan iris-fixated IOL implantation followed to CLE with PC-IOL implantation were encouraging for the correction of extreme hyperopia. Long term follow-up examinations were necessary for further determination of the efficacy and safety of this combinational procedure.