Identification and bioactivity evaluation of twelve previously undescribed depsidone derivatives from Garcinia oligantha.

Phytochemical studies on the leaves and twigs of Garcinia oligantha Merr. led to the isolation of twelve previously undescribed depsidone derivatives (oliganthdepsidones A-L, 1-12). Their structures were elucidated by extensive spectroscopic analysis including 1H and 13C NMR, HSQC, HMBC and NOESY along with HRESIMS. The structures of oliganthdepsidones G and J were finally determined using DFT-NMR chemical shift calculations and DP4+ methods. Cytotoxicity test in four human cancer cell lines indicated that oliganthdepsidone F had relatively strong cytotoxic effect against A375 (melanoma), A549 (lung cancer), HepG2 (liver cancer), and MCF-7 (breast cancer) cell lines with IC50 of 18.71, 15.44, 10.92, and 15.90 µM, respectively. The dose- and time-dependent antiproliferative effects of oliganthdepsidone F on these cell lines were also observed by CCK-8 test. As determined by fluorescent microscopy and flow cytometry in these cell lines, oliganthdepsidone F could promote cell apoptosis, leading to the inhibition of cell proliferation. The results of wound healing assay and transwell assay showed that oliganthdepsidone F could inhibit the migration and invasion of A549 and MCF-7 cell lines in a concentration-dependent manner.

Anti-tumor alkaloids from Peganum harmala.

Six alkaloids peharmalines F-K, along with 14 known ones, were isolated from the aerial part of Peganum harmala L.. The structures of the isolated compounds were determined based on their HR-ESI-MS data, extensive NMR spectroscopic analyses, and ECD calculations. 3-(4-Hydroxyphenyl)quinoline exhibited potent antiproliferative activity against the HepG-2 cell lines with an IC50 value of 3.05 µM. Norharmane displayed a moderate inhibition against A549 and HepG-2 cells with IC50 values of 16.45 µM and 17.27 µM, respectively.

Polyprenylated xanthones from the twigs and leaves of Garcinia nujiangensis and their cytotoxic evaluation.

Inspired by the intriguing structures and bioactivities of polyprenylated xanthones, ten previously undescribed polyprenylated xanthones, nujiangxanthones G-P (1-10), and fifteen known ones (11-25) were isolated from the twigs and leaves of Garcinia nujiangensis. The structures of these compounds were established on the basis of spectroscopic data as well as comparison with the literature. Most of the isolates showed potent cytotoxicity against selected cancer cells. Compound 8 showed the highest effects against MDA-MB-231 and A549 cell lines with IC50 values of 4.12 and 2.67 µM and 16 demonstrated the most potent activity against MCF-7 cell line with an IC50 value of 3.36 µM.

Clinical Observation of the Efficacy of Endoscopic Retrograde Cholangiopancreatography on Elder Choledocholithiasis and Its Effects on the Levels of TNF-α, IL-1, and IL-6.

OBJECTIVE: We conducted this study to investigate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) on elder choledocholithiasis and its effects on the levels of TNF-α, IL-1, and IL-6. METHODS: Elder patients with choledocholithiasis were enrolled in this study, and according to the surgical methods, they were divided into the ERCP group and the surgical group. After treatment, we compared the efficacy of these two methods on patients, inflammatory responses indicated by the levels of TNF-α, IL-1, and IL-6, and the complications. RESULTS: No statistical significance was identified in the difference of the success rate in removal between the two groups (98% vs. 94%), but indicators of the ERCP group, including the surgical duration (28.5±12.8) min, remission duration of abdominal pain (1.2±0.2) d, recession time of jaundice (2.0±0.3) d, postoperative bedridden time (1.4±0.2) d, treatment time of the anti-infection (1.5±0.2) d, length of stay in hospital (6.5±0.3) d, levels of TNF-α (2.1±0.2) µg/L, IL-1 (6.3±0.8) µg/L, IL-6 (2.8±0.3) µg/L, and the incidence rate of complications (1.8%), were all significantly lower than those in the surgical group (p<0.05). CONCLUSION: In the treatment of choledocholithiasis, ERCP is excellent in controlling the trauma, accelerating the recovery duration, reducing the occurrence of complications and ameliorating the inflammatory responses. Thus, it is an ideal choice for choledocholithiasis.

Clinical Observation of the Efficacy of Endoscopic Retrograde Cholangiopancreatography on Elder Choledocholithiasis and Its Effects on the Levels of TNF-α, IL-1, and IL-6

SUMMARY OBJECTIVE: We conducted this study to investigate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) on elder choledocholithiasis and its effects on the levels of TNF-α, IL-1, and IL-6. METHODS: Elder patients with choledocholithiasis were enrolled in this study, and according to the surgical methods, they were divided into the ERCP group and the surgical group. After treatment, we compared the efficacy of these two methods on patients, inflammatory responses indicated by the levels of TNF-α, IL-1, and IL-6, and the complications. RESULTS: No statistical significance was identified in the difference of the success rate in removal between the two groups (98% vs. 94%), but indicators of the ERCP group, including the surgical duration (28.5±12.8) min, remission duration of abdominal pain (1.2±0.2) d, recession time of jaundice (2.0±0.3) d, postoperative bedridden time (1.4±0.2) d, treatment time of the anti-infection (1.5±0.2) d, length of stay in hospital (6.5±0.3) d, levels of TNF-α (2.1±0.2) μg/L, IL-1 (6.3±0.8) μg/L, IL-6 (2.8±0.3) μg/L, and the incidence rate of complications (1.8%), were all significantly lower than those in the surgical group (p<0.05). CONCLUSION: In the treatment of choledocholithiasis, ERCP is excellent in controlling the trauma, accelerating the recovery duration, reducing the occurrence of complications and ameliorating the inflammatory responses. Thus, it is an ideal choice for choledocholithiasis.

RESUMO OBJETIVO: Realizamos este estudo para investigar a eficácia clínica da colangiopancreatografia retrógrada endoscópica (ERCP) na coledocolitíase idosa e seus efeitos nos níveis de TNF-α, IL-1 e IL-6. MÉTODOS: Pacientes idosos com coledocolitíase foram matriculados neste estudo. De acordo com os métodos cirúrgicos, eles foram divididos em grupo ERCP e grupo cirúrgico. Após o tratamento, comparamos a eficácia desses dois métodos em pacientes, respostas inflamatórias indicadas pelos níveis de TNF-α, IL-1 e IL-6 e as complicações. RESULTADOS: Não houve significância estatística na diferença da taxa de sucesso na remoção entre os dois grupos (98% versus 94%), mas indicadores do grupo ERCP, incluindo a duração cirúrgica (28,5 ± 12,8) min, duração da remissão da dor abdominal (1,2 ± 0,2) d, tempo de recessão de icterícia (2,0 ± 0,3) d, tempo pós-operatório (1,4 ± 0,2) d, tempo de tratamento da infecção (1,5 ± 0,2) d, duração da internação (6,5 ± 0,3) d, níveis de TNF-α (2,1 ± 0,2) μg / L, IL-1 (6,3 ± 0,8) μg / L, IL-6 (2,8 ± 0,3) μg / L e a taxa de incidência de complicações (1,8 %) foram todos significativamente inferiores aos do grupo cirúrgico (p<0,05). CONCLUSÃO: No tratamento da coledocolitíase, a ERCP é excelente no controle do trauma, acelerando a duração da recuperação, reduzindo a ocorrência de complicações e melhorando as respostas inflamatórias. Assim, é uma escolha ideal para a coledocolitíase.

New application of phthalocyanine molecules: from photodynamic therapy to photothermal therapy by means of structural regulation rather than formation of aggregates.

Phthalocyanine (Pc) molecules exhibit high extinction coefficients in near-infrared region, rendering them well-suited for phototherapies, but most of their applications are limited to the field of photodynamic therapy (PDT). Herein, for the first time, we illustrate that Pc molecules can be endowed with excellent photothermal properties by means of structural regulation rather than formation of aggregates. Three representative Pc derivatives show efficient activities of photothermal therapy (PTT) against human hepatocellular carcinoma cells. Among them, copper phthalocyanine (PcC1) exhibits a high in vivo PTT efficacy against mice bearing S180 tumors. The unique investigation in this article should light up a perspective of Pc's new applications for PTT, which enable to make up the inherent defects of PDT.

A tumor-targeted activatable phthalocyanine-tetrapeptide-doxorubicin conjugate for synergistic chemo-photodynamic therapy.

Chemo-photodynamic therapy is a promising strategy for cancer treatments. However, it remains a challenge to develop a chemo-photodynamic therapeutic agent with little side effect, high tumor-targeting, and efficient synergistic effect simultaneously. Herein, we report a zinc(II) phthalocyanine (ZnPc)-doxorubicin (DOX) prodrug linked with a fibroblast activation protein (FAP)-responsive short peptide with the sequence of Thr-Ser-Gly-Pro for chemo-photodynamic therapy. In the conjugate, both photosensitizing activity of ZnPc and cytotoxicity of DOX are inhibited obviously. However, FAP-triggered separation of the photosensitizer and DOX can enhance fluorescence emission, singlet oxygen generation, dark- and photo-cytotoxicity significantly, and lead to a synergistic anticancer efficacy against HepG2 cells. The prodrug can also be specifically and efficiently activated in tumor tissue of mice. Thus, this prodrug shows great potential for clinical application in chemo-photodynamic therapy.

Overexpression of immunoglobulin G prompts cell proliferation and inhibits cell apoptosis in human urothelial carcinoma.

Only B lymphocytes can express immunoglobulins according to the traditional immunological theories, and the expression of immunoglobulin G (IgG) messenger RNA (mRNA) and protein was found in certain human cancer cells recently. However, the expression pattern of IgG and its possible role in human urothelial carcinoma are still elusive. In this study, we investigated the expression of IgG in two human urothelial carcinoma cell lines, T24 and BIU-87, and in 56 cases of clinical urothelial carcinoma tissues. The mRNA of IgG was positively detected by in situ hybridization and reverse transcription PCR; furthermore, IgG protein was also positively detected by immunohistochemistry and Western blot. Moreover, blockade of tumor-derived IgG by either antihuman IgG antibody or antisense oligonucleotides increased cell apoptosis and inhibited cell growth in bladder cancer cell lines in vitro, and antihuman IgG antibody could suppress the growth of xenotransplant tumor in vivo. In addition, either antihuman IgG antibody or antisense oligonucleotides enhanced the sensitivity to mitomycin C in bladder cancer cell line T24. Furthermore, blockade of IgG in bladder cancer cell T24 resulted in upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. Our results indicated that bladder cancer cells were capable of expressing IgG, and blockade of IgG expression induced cell apoptosis through activation of caspase-dependent pathway. A novel potential targeted therapy for bladder cancer will be possibly developed based on these data.

Pituitary adenylate cyclase activating-peptide and its receptor antagonists in development of acute pancreatitis in rats.

AIM: Pituitary adenylate cyclase activating-peptide (PACAP) is a late member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family of brain-gut peptides. It is unknown whether PACAP takes part in the development of acute pancreatitis and whether PACAP or its antagonists can be used to suppress the progression of acute pancreatitis. We investigated the actions of PACAP and its receptor antagonists in acute pancreatitis on rats. METHODS: Acute pancreatitis was induced in rats with caerulein or 3.5% sodium taurocholate. The rats were continuously infused with 5-30 microg/kg PACAP via jugular vein within the first 90 min, while 10-100 microg/kg PACAP6-27 and (4-Cl-D-Phe6, Leu17) VIP (PACAP receptor antagonists) were intravenously infused for 1 h. Biochemical and histopathological assessments were made at 4 h after infusion. Pancreatic and duodenal PACAP concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Chinese ink-perfused pancreas was fixed, sectioned and cleared for counting the functional capillary density. RESULTS: PACAP augmented caerulein-induced pancreatitis and failed to ameliorate sodium taurocholate-induced pancreatitis. ELISA revealed that relative concentrations of PACAP in pancreas and duodenum were significantly increased in both sodium taurocholate- and caerulein-induced pancreatitis compared with those in normal controls. Unexpectedly, PACAP6-27 and (4-Cl-D-Phe6, Leu17) VIP could induce mild acute pancreatitis and aggravate caerulein-induced pancreatitis with characteristic manifestations of acute hemorrhagic/necrotizing pancreatitis. Functional capillary density of pancreas was interpreted in the context of pancreatic edema, and calibrated functional capillary density (calibrated FCD), which combined measurement of functional capillary density with dry weight/wet weight ratio, was introduced. Hyperemia or congestion, rather than ischemia, characterized pancreatic microcirculatory changes in acute pancreatitis. CONCLUSION: PACAP may take part in the pathogenesis of acute pancreatitis in rats. The two PACAP receptor antagonsits might act as partial agonists. Calibrated functional capillary density can reflect pancreatic microcirculatory changes in acute pancreatitis.

Effect of inducible cyclooxygenase expression on local microvessel blood flow in acute interstitial pancreatitis.

OBJECTIVE: To investigate the role of inducible cyclooxygenase (COX-2) mRNA expression in local microvessels in rats with acute interstitial pancreatitis (AIP) induced by caerulein injection. METHODS: The reverse transcription polymerase chain reaction (RT-PCR) was used to detect COX-2 gene expression in pancreatic tissue. Parameters of acute pancreatitis, such as serum amylase (AMS) and plasma myeloperoxidase (MPO) activities, were assayed using spectrophotometry. Intravital fluorescence microscopy with fluorescein isothiocyanate-labelled erythrocytes was used to study the pancreatic microvessels of rats with AIP and normal control rats. RESULTS: Highly significant increases in COX-2 expression and AMS and MPO activity were seen in rats with AIP compared with controls. After caerulein injection, pancreatic capillary blood flow was decreased (4 hours, p > 0.05; 8 hours, p < 0.001), functional capillary density was reduced (4 hours, p > 0.05; 8 hours, p < 0.001), and there was irregular and intermittent capillary perfusion at 8 hours. There was also a positive correlation between the level of COX-2 expression and MPO activity (plasma, r = 0.5449, p < 0.05; tissue, r = 0.5698, p < 0.05). CONCLUSIONS: The correlations between increased COX-2 expression and decreased capillary perfusion and blood flow and increased oedema following AIP may show that COX-2 expression can induce neutrophil sequestration to the pancreas, which may be one of the cascading inflammatory factors in the development of AIP.