Frajunolides L–O, Four New 8-Hydroxybriarane Diterpenoids from the Gorgonian Junceella fragilis

Four new 8-hydroxybriarane diterpenoids, frajunolides L–O (1–4), were isolated from the Taiwanese gorgonian Junceella fragilis. The structures of compounds 1–4 were elucidated based on spectroscopic analysis, especially 2D NMR (1H-1H COSY, HSQC, HMBC and NOESY) and HRMS. Compounds 1 and 4 showed weak anti-inflammatory activity as tested by superoxide anion generation and elastase release by human neutrophil in response to fMLP/CB. Compound 3 showed selective inhibition on elastase release in vitro

Burkitt's Lymphoma Mimicking a Primary Gynecologic Tumor

SummaryObjectiveBurkitt's lymphoma (BL) occurs mostly in children; bilateral ovarian involvement mimicking a gynecologic malignancy in adults is extremely rare. Here, we report a patient with BL mimicking a gynecologic tumorCase ReportA 50-year-old Taiwanese woman presented with the complaint of persistent lower abdominal distension with dull pain, easy satiety, and progressively increasing abdominal girth for 2 weeks. Amenorrhea was also noted for about 2 months, and her review of systems was negative for the common “B” symptoms associated with lymphoma. At our hospital, imaging studies revealed a huge pelvic mass (10.8 ×8.7 cm), suggesting a large subserous myoma or an ovarian tumor. Under the impression of pelvic mass, she underwent exploratory laparotomy. Primary ovarian sex-cord malignancy with cecum involvement was impressed by the primitive intraoperative frozen section report. Subsequently, an optimal cytoreductive operation with right hemicolectomy was performed. However, final histopathologic report was an extranodal multifocal BL.ConclusionAlthough extranodal BL in ovaries is a rare condition, it should be noted in the differential diagnosis of pelvic gynecologic malignancies

Cumingianoside A, a Phyto-Triterpenoid Saponin Inhibits Acquired BRAF Inhibitor Resistant Melanoma Growth via Programmed Cell Death

Mutated proto-oncogene BRAF is a bona fide therapeutic target for melanomas. Regrettably, melanoma acquires resistance to BRAF inhibitors, e.g., vemurafenib (PLX4032) casting doubt on this promising melanoma targeted therapy. In this study, we explored the bioactivity of triterpenoid saponin cumingianoside A (CUMA), isolated from leaves and twigs of Dysoxylum cumingianum against PLX4032-resistant BRAFV 600E mutant melanoma A375-R in vitro and in vivo. Our data show that CUMA treatment inhibited A375-R melanoma cell proliferation in a time- and dose-dependent manner. CUMA also suppressed the activity of CDK1/cyclin B1 complex and led to G2/M-phase arrest of A375-R cells. Furthermore, CUMA treatment resulted in induction of apoptosis as shown by the increased activation of caspase 3 and caspase 7, and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). We also observed that CUMA induced autophagy-like activity in A375-R cells, as shown by the increased expression of autophagy-related genes and increased formation of autophagosomes. Moreover, we found that CUMA treatment induced ER stress response and co-treatment with an ER stress inhibitor (4-PBA) could attenuate apoptosis induced by CUMA. Importantly, orally administered CUMA as a single agent or in combination with PLX4032 exhibited strong tumor growth inhibition in a PLX4032-resistant A375-R xenograft mouse model, and with little toxicity. This is the first report to explore the anti-tumor activity of CUMA in vitro and in vivo mechanistically, and our results imply that this triterpenoid saponin may be suitable for development into an anti-melanoma agent

Synthesis of 1-Substituted Carbazolyl-1,2,3,4-tetrahydro- and Carbazolyl-3,4-dihydro-β-carboline Analogs as Potential Antitumor Agents

A series of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-β-carboline analogs have been synthesized and evaluated for antitumor activity against human tumor cells including KB, DLD, NCI-H661, Hepa, and HepG2/A2 cell lines. Among these, compounds 2, 6, 7, and 9 exhibited the most potent and selective activity against the tested tumor cells. As for inhibition of topoisomerase II, compounds 1–14 and 18 showed better activity than etoposide. Among them, compounds 3, 4, 7, 9, and 10 exhibited potent activity. The structure and activity relationship (SAR) study revealed correlation between carbon numbers of the side chain and biological activities. The molecular complex with DNA for compound 2 was proposed

Burkitt's Lymphoma Mimicking a Primary Gynecologic Tumor

SummaryObjectiveBurkitt's lymphoma (BL) occurs mostly in children; bilateral ovarian involvement mimicking a gynecologic malignancy in adults is extremely rare. Here, we report a patient with BL mimicking a gynecologic tumorCase ReportA 50-year-old Taiwanese woman presented with the complaint of persistent lower abdominal distension with dull pain, easy satiety, and progressively increasing abdominal girth for 2 weeks. Amenorrhea was also noted for about 2 months, and her review of systems was negative for the common “B” symptoms associated with lymphoma. At our hospital, imaging studies revealed a huge pelvic mass (10.8 ×8.7 cm), suggesting a large subserous myoma or an ovarian tumor. Under the impression of pelvic mass, she underwent exploratory laparotomy. Primary ovarian sex-cord malignancy with cecum involvement was impressed by the primitive intraoperative frozen section report. Subsequently, an optimal cytoreductive operation with right hemicolectomy was performed. However, final histopathologic report was an extranodal multifocal BL.ConclusionAlthough extranodal BL in ovaries is a rare condition, it should be noted in the differential diagnosis of pelvic gynecologic malignancies

Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia

Obstructive sleep apnea is mainly characterized by intermittent hypoxia (IH), which is associated with hyperreactive airway diseases and lung inflammation. Sensitization of lung vagal C fibers (LVCFs) induced by inflammatory mediators may play a central role in the pathogenesis of airway hypersensitivity. In females, estrogen interferes with inflammatory signaling pathways that may modulate airway hyperreactivity. In this study, we investigated the effects of IH on the reflex and afferent responses of LVCFs to chemical stimulants and lung inflammation in adult female rats, as well as the role of estrogen in these responses. Intact and ovariectomized (OVX) female rats were exposed to room air (RA) or IH for 14 consecutive days. On day 15, IH enhanced apneic responses to right atrial injection of chemical stimulants of LVCFs (e.g., capsaicin, phenylbiguanide, and α,β-methylene-ATP) in intact anesthetized females. Rats subjected to OVX prior to IH exposure exhibited an augmented apneic response to the same dose of stimulants compared with rats subjected to other treatments. Apneic responses to the stimulants were completely abrogated by bilateral vagotomy or perivagal capsaicin treatment, which blocked the neural conduction of LVCFs. Electrophysiological experiments revealed that in IH-exposed rats, OVX potentiated the excitability of LVCFs to stimulants. Moreover, LVCF hypersensitivity in rats subjected to OVX prior to IH exposure was accompanied by enhanced lung inflammation, which was reflected by elevated inflammatory cell infiltration in bronchoalveolar lavage fluid, lung lipid peroxidation, and protein expression of inflammatory cytokines. Supplementation with 17β-estradiol (E2) at a low concentration (30 μg/ml) but not at high concentrations (50 and 150 μg/ml) prevented the augmenting effects of OVX on LVCF sensitivity and lung inflammation caused by IH. These results suggest that ovarian hormones prevent the enhancement of LVCF sensitivity and lung inflammation by IH in female rats, which are related to the effect of low-dose estrogen

Blockchain-Based Medical Record Management with Biofeedback Information

Blockchain is a new emerging technology of distributed databases, which guarantees the integrity, security and incorruptibility of data by means of the cryptography. Such features are suitable for secure and reliable data storage. This chapter investigates the blockchain-based architecture with applications to medical health record or biofeedback information management. This framework employs the smart contract to establish a medical record management system to ensure the privacy of patients. Moreover, the blockchain technique accelerates the medical record or information exchange such that the cost of human resource is significant reduced. All patients can manage their individual medical records and information easily in the different hospitals and clinics. They also have the privilege to deal with and authorize personal medical records in the proposed management framework

14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β

[[abstract]]Background: Pluripotent embryonic stem cells are considered to be an unlimited cell source for tissue regeneration and cell-based therapy. Investigating the molecular mechanism underlying the regulation of embryonic stem cell expansion is thus important. 14-3-3 proteins are implicated in controlling cell division, signaling transduction and survival by interacting with various regulatory proteins. However, the function of 14-3-3 in embryonic stem cell proliferation remains unclear. Methodology and Principal Findings: In this study, we show that all seven 14-3-3 isoforms were detected in mouse embryonic stem cells. Retinoid acid suppressed selectively the expression of 14-3-3σ isoform. Knockdown of 14-3-3σ with siRNA reduced embryonic stem cell proliferation, while only 14-3-3σ transfection increased cell growth and partially rescued retinoid acid-induced growth arrest. Since the growth-enhancing action of 14-3-3σ was abrogated by β-catenin knockdown, we investigated the influence of 14-3-3σ overexpression on β-catenin/GSK-3β. 14-3-3σ bound GSK-3β and increased GSK-3β phosphorylation in a PI-3K/Akt-dependent manner. It disrupted β-catenin binding by the multiprotein destruction complex. 14-3-3σ overexpression attenuated β-catenin phosphorylation and rescued the decline of β-catenin induced by retinoid acid. Furthermore, 14-3-3σ enhanced Wnt3a-induced β-catenin level and GSK-3β phosphorylation. DKK, an inhibitor of Wnt signaling, abolished Wnt3a-induced effect but did not interfere GSK-3β/14-3-3σ binding. Significance:Our findings show for the first time that 14-3-3σ plays an important role in regulating mouse embryonic stem cell proliferation by binding and sequestering phosphorylated GSK-3β and enhancing Wnt-signaled GSK-3β inactivation. 14-3-3σ is a novel target for embryonic stem cell expansion