Randainins A-D, Based on Unique Diterpenoid Architectures, from Callicarpa randaiensis.

Four new compounds, randainins A-D (1-4), were isolated from the leaves and twigs of Callicarpa randaiensis, which is an endemic species in Taiwan. Compounds 1 and 2 are diterpenoids with an unusual trans-7/5 ring system, whereas compounds 3 and 4 are diterpenoids possessing a trans-5/7 ring scaffold. The structures of the new compounds were established based on NMR and MS data analyses. Anti-inflammatory activities and cytotoxicity were tested and evaluated for these compounds. Compound 4 exhibited moderate inhibition of superoxide-anion generation with an IC50 value of 21.5 ± 2.5 µM.

Cespitulones A and B, cytotoxic diterpenoids of a new structure class from the soft coral Cespitularia taeniata.

Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between C-20 and C-11. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against human medulloblastoma and colon adenocarcinoma cancer cells.

Anti-liver fibrotic lignans from the fruits of Schisandra arisanensis and Schisandra sphenanthera.

Three new polyoxygenated C(18)-dibenzocyclooctadiene lignans, arisanschinins M and N (1 and 2) and schisphenin A (3), together with eight related metabolites (4-11), were isolated from the fruits of Schisandra arisanensis and Schisandra sphenanthera, respectively. The structures of 1-3 were elucidated on the basis of extensive spectroscopic and 2D NMR (HSQC, HMBC, and NOESY) analyses. The configuration of the biphenyl moiety in the octadiene ring was determined by circular dichroism (CD). Compound 1 possessed an unprecedented 3-(1-hydroxypropan-2-yl)-3-methyl-1,4-dioxo-2-one lactonide ring system attaching at C-6/C-14. Pharmacological studies revealed that compounds 3, 4, 6, 7, and 10 exhibited significant anti-hepatic fibrosis activity, while 9 and 11 showed cytotoxicity against HSC-T6 cells. The biogenetic pathway for compound 1 was also proposed.

Four new briarane diterpenoids from Taiwanese gorgonian Junceella fragilis.

Four new 8-hydroxybriarane diterpenoids, frajunolides P-S (1-4), together with umbraculolide A, juncenolide C, junceellonoid A and juncin R, were isolated from the acetone extract of the gorgonian Junceella fragilis, collected from the southeast coast of Taiwan. Compound 1 contains an unusual pivaloyloxy group at C-2, while 3 is a rare compound having a chlorine atom on the olefinic carbon (C-6). The structures of the isolated compounds were established by extensive spectroscopic analysis, including 1D- and 2D-NMR, as well as HRMS data. Compound 1 was further confirmed by X-ray crystallographic analysis. In the anti-inflammatory test, compounds 1 and 2 exhibited moderate inhibition on superoxide anion generation and elastase release by human neutrophils in response to formylmethionylleucyl-phenylalanine/dihydrocytochalasin B (fMLP/CB).

Clinical Characteristics and Treatment Outcomes of Oral Cancers Using Transoral Robotic Surgery in an Endemic Region.

Oral cancer poses a major health challenge in Taiwan, consistently ranking among the highest globally in both incidence and cancer-related mortality. Transoral robotic surgery (TORS) has potential advantages over open surgery, but its long-term oncologic outcomes are not well established. In this study, we sought to elucidate the role of TORS in improving treatment outcomes among oral cancer patients. A case-control study with propensity score matching was conducted in a single teaching hospital in Taiwan. It included 72 oral cancer patients in each group to analyze and compare survival outcomes between the surgical approaches. The TORS group demonstrated a higher negative resection margin rate, a lower mortality risk and better overall survival than the open-surgery group. Multivariate Cox regression analysis confirmed TORS's association with a reduced risk of death. Kaplan-Meier survival analysis and log-rank tests indicated significantly better survival outcomes for the TORS group across all cancer stages. Moreover, the TORS group exhibited improved overall survival rates for stage III and IV patients compared to the conventional open-surgery group. In conclusion, this study suggests that TORS may offer better overall survival rates and potential advantages over conventional surgery for oral cancer treatment.

Bioactive diterpenes from Callicarpa longissima.

Investigation of the leaves and twigs of Callicarpa longissima resulted in the isolation of four new compounds (1-4), callilongisins A-D, and five known compounds, ursolic acid, 3-oxoanticopalic acid, (E)-6ß-hydroxylabda-8(17),13-dien-15-oic acid, 5-hydroxy-3,6,7,4'-tetramethoxyflavone, and artemetin. Compounds 1-3 are 3,4-seco-abietane-type diterpenoids, and compound 4 is an analogue of a labdenoic-type diterpene. The structure of compound 1 was confirmed by X-ray crystallographic analysis. Cytotoxicity against a human prostate cancer cell line (PC3) and anti-inflammatory activities of the isolated compounds were evaluated.

Endovascular treatment of a huge cervical carotid artery pseudoaneurysm with Wallgraft prosthesis.

Traumatic pseudoaneurysm of the internal carotid artery (ICA) is a rare cause of epistaxis, which may be life-threatening if left untreated. We report the case of a massive epistaxis from left ICA pseudoaneurysm. Our patient was a 38 year-old man with the history of a severe traffic accident 13 years ago. The pseudoaneurysm was treated with the placement of a Wallgraft prosthesis inside the carotid artery. After the endovascular treatment, the left ICA remained patent and no recurrent hemorrhage was noted in the 1 year follow up after the procedure.

Bioactive xenicane diterpenoids from the Taiwanese soft coral Asterospicularia laurae.

Chemical investigation of the Taiwanese soft coral Asterospicularia laurae has led to the isolation of three new xenicane diterpenoids, named asterolaurins K-M (1-3, resp.). Their chemical structures were determined through extensive spectroscopic analyses ((1) H- and (13) C-NMR, (1) H,(1) H-COSY, HMBC, and NOESY). Compound 2 exhibited cytotoxic activity against HEp-2, Daoy, MCF-7, and WiDr tumor cells.

Diastereomeric identification of neolignan rhamnosides from Trochodendron aralioides leaves by LC-SPE-NMR and circular dichroism.

Trochodendron aralioides is an old-existing relic plant with limited availability and only a few identified compounds. Accumulative analysis on the methanolic extract from its leaf part by LC-SPE-NMR resulted in the identification of seven new compounds, including three neolignan α-rhamnosides [(7R,8S)-dihydrodehydrodiconiferyl alcohol- 9-O-α-rhamnopyranoside (2) and 9'-O-α-rhamnopyranoside (3), and (7S,8R)-dehydrodiconiferyl alcohol-9'-O-α-rhamnopyranoside (4)], two isomeric oxyneolignan α-rhamnosides [(7R,8S)- (5) and (7R,8R)-icariside E8 (6)), and (7R,8S)- (10) and (7R,8R)-icariside E9 (11)], and two isomeric acylated fructofuranosyl mevalonolactones (13, 14), along with five known compounds (1, 7-9 and 12). The absolute configuration of the C-7 and C-8 positions for the new compounds 2-6 and 10-11 was assigned by comparison of the reported ECD spectra. Compounds 2, 3, 4, and 6 were further isolated by semi-preparative column chromatography for structure confirmation by 2D NMR spectroscopic analysis.

alpha-Glucosidase inhibitors from the seeds of Syagrus romanzoffiana.

Bioassay-guided fractionation against alpha-glucosidase resulted in isolation and characterization of eight active compounds from the EtOH extract of the seeds of Syagrus romanzoffiana. Of these, seven are stilbenoids, and two of them, 13-hydroxykompasinol A (1) and scirpusin C (4), possess potent inhibitory activity against alpha-glucosidase type IV from Bacillus stearothermophilus with the IC50 value of 6.5 and 4.9 microM, respectively. The in vivo assay on normal Wistar rats using oral sucrose challenge also demonstrated that kompasinol A (2) and 3,3',4,5,5'-pentahydroxy-trans-stilbene (5) possess significant effect in reducing the postprandial blood glucose level (10.2% and 12.1% at 10mg/kg, respectively). These results suggest that stilbenoids might be explored for their therapeutic potential as hypoglycemic agents.

Cespihypotins Q-V, verticillene diterpenoids from Cespitularia hypotentaculata.

Chemical investigation of the soft coral Cespitularia hypotentaculata resulted in the isolation of six new diterpenes, cespihypotins Q-V. The new metabolites comprised five verticillane-type diterpenes and one nor-verticillane derivative. Their structures were determined through detailed spectroscopic analyses, especially HRESIMS and 2D NMR techniques. The relative configuration was deduced by interpretation of NOESY spectra. Cespihypotin T exhibited significant cytotoxic activity against human Daoy and WiDr tumor cell lines.

Small mutations of the DMD gene in Taiwanese families.

BACKGROUND/PURPOSE: Duchenne/Becker muscular dystrophies are X-linked recessive disorders caused by mutations in the Duchenne muscular dystrophy (DMD) gene. We aimed to demonstrate the small mutation patterns of the DMD gene in Taiwanese subjects. METHODS: We sequenced all 79 exons of the DMD gene in 33 unrelated Taiwanese families in which large-scale deletions and duplications had been excluded by multiplex ligation-dependent probe amplification. RESULTS: Direct sequencing detected 23 different mutations from 26 families, including 15 novel mutations and eight previously reported ones. The 15 novel mutations consisted of seven substitutions (c.1238C>G [p.S413X], c.2971G>T [p.E991X], c.3172C>T [p.Q1058X], c.7402G>T [p.E2468X], c.8022C>G [p.S2605X], c.10018T>C [p.C3340R], c.10546G>T [p.E3516X]), six small deletions (c.2202delG [p.A668fsX676], c.2268delC [p.F756fsX759], c.4611delT [p.N1537fsX1545], c.4856_4857delAA [p.K1619fsX1621], c.6638delT [p.L2213fsX2220], c.9457delT [p.C3153fsX3154]), and two small insertions (c.4351insA [p.L1451fsX1468], c.10493_10495insAAT [p.L3498X]). Twenty-two of the 23 pathologic changes disrupted the translational reading frame (13 nonsense, 7 frameshift, 2 splice-site change), whereas only one was a missense variant with known pathogenic nature. Two previously reported mutations, c.8038C>T [p.R2680X] and c.10108C>T [p.R3370X] were detected in two and three unrelated families, respectively. CONCLUSION: Most identified mutations either led to a predictable premature stop codon or resulted in splicing defects, which caused defective function of dystrophin. Our findings extend the mutation spectrum of the DMD gene. Molecular characterization of the affected families is important for genetic counseling and prenatal diagnosis.

Molecular characterization of a beta-globin gene deletion of 1357 bp in a Taiwanese beta-thalassemia carrier.

A 30-year-old male had hypochromic microcytosis and elevated Hb F and Hb A(2) levels (MCV 72.5 fL, MCH 25.2 pg, Hb F 8.9% and Hb A(2) 6.6%). Direct DNA sequencing of the entire beta-globin gene revealed no anomalies. Multiplex ligation-dependent probe amplification (MLPA) showed reduced signals at probes for the promoter, 5'UTR (5' untranslated region), exon 2 and intron 2 regions of the beta-globin gene. Gap-polymerase chain reaction (gap-PCR) successfully obtained junctional fragments. Direct sequencing of the gap-PCR product revealed that the 5' breakpoint was located at -548 (relative to the Cap site of the beta-globin gene) and the 3' breakpoint was located at +810 in the second intron of the beta-globin gene. A total of 1357 bp were deleted (NG_000007.3:g.69997_71353del1357). Similar to another two beta-globin gene deletions reported in Black and Croatian thalassemia carriers, respectively, this deletion was the result of a non homologous breakage and reunion event.

Recurrent autoimmune inner ear disease (AIED) and polyarteritis nodosa in a patient with large cell lung carcinoma.

Autoimmune inner ear disease (AIED) is a very rare disorder with distinct clinical features and can occur in patients with malignancy or autoimmune diseases. We report a 72-year-old male patient with polyarteritis nodosa treated continuously for 5 years with aggressive immunosuppressive drugs, including cyclophosphamide, who experienced three episodes of acute hearing loss during treatment. Organic lesions of the external and middle ear were excluded by repeated examinations, and if one subscribes to McCabe's (Ann Otol Rhinol Laryngol 88:585-589, 1979) definition of AIED, this condition must be considered as the likely cause of the hearing loss. During the period of treatment, three episodes of AIED occurred, and eventually, lung cancer developed. From the time relationship and clinical manifestations of neuropathy and livedo reticularis, the first episode of hearing loss was more likely to be related to vasculitis itself, while the third episode may well have been associated with the development of lung cancer given the dramatic improvement in the clinical condition following treatment of the tumor by excision and cancer chemotherapy. Coexistence of AIED, vasculitis, and malignancy in the same patient has only been reported infrequently, and our case suggests that this coexistence may not be coincidental. For those patients with autoimmune disease who are on long-term immunosuppressive drug therapy, active surveillance for a nascent malignant tumor should be exercised if AIED recurs or persists.

Multiplex ligation-dependent probe amplification identification of deletions and duplications of the Duchenne muscular dystrophy gene in Taiwanese subjects.

BACKGROUND/PURPOSE: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations in the DMD gene. We intended to determine the distribution of DMD gene deletions and duplications in local Taiwanese male patients and potential female carriers. METHODS: A total of 102 unrelated subjects, including 89 unrelated DMD/BMD male patients and another 13 unrelated potential female carriers, were recruited for this study. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect DMD gene deletions and duplications in the 102 subjects. RESULTS: MLPA was informative in 60.7% (54/89) of these patients, identifying deletions in 36.0% (32/89) and duplications in 24.7% (22/89) of these patients. This assay revealed deletions in 30.8% (4/13) and duplications in 30.8% (4/13) of the 13 potential carriers. Deletions and duplications were detected in 35.3% (36/102) and 25.5% (26/102) of a total of 102 affected families, respectively in this series. The "hotspot" regions of the duplications were close to those of the deletions. CONCLUSION: MLPA was proven to be a powerful tool for the detection of DMD gene deletions and duplications in male patients and female carriers. There was a relatively lower frequency of deletion and a higher frequency of duplication of DMD gene in this population compared to previous reports.

Chemical constituents from Phoebe minutiflora II.

Two new lignans were isolated from Phoebe minutiflora, namely 8'-epiaristotetralone (1) and 8'-epiaristoligone (2), together with seven known compounds. Their structures and absolute stereochemistry were determined by spectral analysis (NMR and CD) and chemical correlation.

Copy number analysis of survival motor neuron genes by multiplex ligation-dependent probe amplification.

PURPOSE: To determine the copy number of survival motor genes using multiplex ligation-dependent probe amplification. METHODS: Three hundred seventy-three subjects were recruited and divided into three groups. Group 1 included 310 subjects without a history of muscular atrophy, Group 2 consisted of 18 patients and 45 carriers of spinal muscular atrophy, and Group 3 included 20 subjects who were previously tested with denatured high-performance liquid chromatography. The copy number of survival motor neuron 1 and survival motor neuron 2 genes was determined with a commercially available multiplex ligation-dependent probe amplification kit. RESULTS: Twenty-one genotypes of the survival motor neuron genes could be clearly defined in this series. The whole process of genotyping took <48 hours. In Group 1, 2:2 (survival motor neuron 1:survival motor neuron 2) was most common (52.90%), followed by 2:1 (30.32%); six (1.94%) subjects were found to be carriers of 1:2 or 1:3. In Group 2, all 18 patients had zero copies of the survival motor neuron 1 gene and variable copies of the survival motor neuron 2 gene. In Group 3, three subjects who had been told they were carriers of spinal muscular atrophy turned out to be noncarriers by multiplex ligation-dependent probe amplification. All 51 carriers from Groups 1 and 2 had one copy of the survival motor neuron 1 gene and one to four copies of the survival motor neuron 2 gene. CONCLUSION: Multiplex ligation-dependent probe amplification is a simple and efficient method for copy number analysis of survival motor neuron genes. It can be used to detect the homozygous and heterozygous survival motor neuron deletion of spinal muscular atrophy.

Preparation and anti-inflammatory activities of diarylheptanoid and diarylheptylamine analogs.

Seven diarylheptylamine (12a-g) and four diarylheptanoid analogs (3-5, 9), structurally related to the natural anti-inflammatory agent oregonin (1), have been prepared from curcumin (2) for evaluation of their activity against the expression of iNOS and COX-2. Diarylheptylamine 12b and diarylheptanoid analogs can inhibit iNOS and COX-2 responses of LPS, although less potently than 1. These compounds, however, possess stronger potency than 1 against COX-2-derived PGE2 formation, of which hexahydrocurcumin (4) is the most potent one with an IC50 value of 0.7 microM.