The Potential Role of Virus Infection in the Progression of Thyroid Cancer.

Multiple factors have engaged in the progression of thyroid cancer (TC). Recent studies have shown that viral infection can be a critical factor in the pathogenesis of TC. Viruses, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may play an essential role in the occurrence, development, and even prognosis in TC. This review mainly explored the potential role of viral infection in the progress of TC. The possible mechanisms could be recognizing the host cell, binding to the receptors, affecting oncogenes levels, releasing viral products to shape a beneficial environment, interacting with immune cells to induce immune evasion, and altering the pituitary-thyroid axis. Thus, comprehensive knowledge may provide insights into finding molecular targets for diagnosing and treating virus-related TC.

Isolation and absolute configuration of alkylpyridine alkaloids from the marine sponge Hippospongia lachne.

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.

Potential regulatory role of the Nrf2/HMGB1/TLR4/NF-κB signaling pathway in lupus nephritis.

OBJECTIVES: Systemic lupus erythematosus is an autoimmune disease that involves multiple organ systems. One of its major complications, lupus nephritis (LN), is associated with a high mortality rate, and children-onset LN have a more severe course and worse prognosis than adults. Oxidative stress and inflammatory responses are involved in LN development and pathogenesis. Thus, this study aimed to explore the role of signaling regulation of the Nrf2/HMGB1/TLR/NF-κB pathway in LN pathogenesis and unravel the expression of TLR4+CXCR4+ plasma cells subset (PCs) in LN. METHODS: C57BL/6 and MRL/lpr mice were divided into four groups: control, model, vector control, and Nrf2 overexpression groups. The vector control and Nrf2 overexpression groups were injected with adenoviral vectors into the kidney in situ. Pathological changes in kidney tissues were observed by hematoxylin-eosin staining. The expression of Nrf2, HMGB1, TLR4, NF-κB, and downstream inflammatory factors in kidney samples was analyzed by quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The ratios of TLR4+CXCR4+ PC subsets in the blood and kidneys of mice were determined by flow cytometry. RESULTS: In MRL/lpr mice, Nrf2 was downregulated while HMGB1/TLR4/NF-κB pathway proteins were upregulated. Nrf2 overexpression decreased the expression of HMGB1, TLR4, NF-κB, and its downstream inflammatory cytokines (IL-1ß and TNFα). These cytokines were negatively correlated with an increase in Nrf2 content. PC and TLR4 + CXCR4 + PCs in the blood and kidney samples were significantly increased in MRL/lpr mice; however, they were decreased upon Nrf2 overexpression. CONCLUSION: This study showed severe kidney injury in an LN mouse model and an increased ratio of TLR4 + CXCR4 + PCs. Furthermore, we observed that Nrf2 regulates LN immune response through the Nrf2/HMGB1/TLR4/NF-κB pathway, which can be considered an important target for LN treatment. The clinical value of the findings of our study requires further investigation.

Hipposponols A and B, two new 9, 11-secosterols from the marine sponge Hippospongia lachne de Laubenfels.

Two new 9,11-secosterols, hipposponols A (1) and B (2), together with five known analogues, aplidiasterol B (3), (3ß,5α,6ß)-3,5,6-triol-cholest-7-ene (4), (3ß,5α,6ß,22E)-3,5,6-triol-ergosta-7,22-diene (5), and one pair of inseparable C-24 epimers of (3ß,5α,6ß,22E)-3,5,6-triol-stigmasta-7,22-diene (6/7), were isolated from the marine sponge Hippospongia lachne de Laubenfels. The structures of isolated compounds were extensively elucidated based on HRESIMS and NMR data. Compounds 2 - 5 showed cytotoxicity against PC9 cells with IC50 values ranging from 34.1 ± 0.9 to 38.9 ± 1.0 µM and compound 4 displayed cytotoxicity against MCF-7 cells with IC50 value of 39.0 ± 0.4 µM.

[Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures].

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

Rare Cases of Bronchial Aneurysm and Comparison of Interventional Embolization in the Treatment of True Bronchial Aneurysm and Pseudobronchial Aneurysm.

Background: Bronchial artery aneurysm (BAA) is a rare disease. Rupture of BAA can lead to life-threatening hemoptysis, and once diagnosed, treatment is needed regardless of symptoms. Transcatheter artery embolization is the first choice of treatment because it is minimally invasive and effective. This study aimed to retrospectively compare the embolization treatment of a case of true BAA and that of a pseudobranchial aneurysm and explore the choice of embolization method for BAA with short neck or no neck. Materials and Methods: Embolization treatment and imaging characteristics of one case of true BAA and one case of pseudobronchial aneurysm admitted to our hospital were analyzed retrospectively. Embolization methods and therapeutic effects of two cases of BAAs were compared. Results: Case 1 was that of an intact true BAA inside the mediastinum located at the opening of the bronchial artery. The distal end of the aneurysm was embolized, and tumor cavity was occluded. No recurrence of BAA was found after the operation. Case 2 was that of a ruptured and hemorrhagic pseudobronchial aneurysm of the mediastinum. Coil embolization combined with covered stent graft exclusion of the thoracic aorta were performed, and the left bronchial artery and BAA were almost occluded. Nine months postoperatively, the mediastinal hematoma was almost completely absorbed. Conclusion: Endovascular embolization has become the most commonly used for the treatment of BAA. Different methods should be selected according to the location and nature of the aneurysm.

Gephyyamycin and cysrabelomycin, two new angucyclinone derivatives from the Streptomyces sp. HN-A124.

Gephyyamycin (1) owned the rare 3,12a-epoxybenz[a]anthracene ring system, and cysrabelomycin (2) possessed an acetylated cysteine group, two new angucyclinone derivatives were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. HN-A124, an actinobacterium isolated from the marine sediments collected from Hainan Province, China. Their structures were elucidated on the basis of MS, NMR spectroscopic, X-ray diffration data analyses and quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compound 2 appeared to show moderate cytotoxicity against human prostate cancer PC3 and human ovarian carcinoma A2780 cell lines with IC50 values of 19.39 and 10.23 µM, respectively; on the other hand, compound 2 also exhibited moderate antibacterial activities against Staphylococcus aureus and Candida albicans with an MIC value of 20.0 and 20 µM, respectively.

lncRNA SNHG1 Promotes Progression of Cervical Cancer Through miR-195/NEK2 Axis.

OBJECTIVE: Cervical cancer is a common gynecologic cancer, and no study has been reported on the way through which lncRNA SNHG1, miR-195 and NEK2 jointly affect cervical cancer cells (CCCs), so this paper will explore a new approach to the development of cervical cancer in this respect. METHODS: Altogether 72 cervical cancer tissues and 54 adjacent tissues were collected. qPCR was performed to quantify lncRNA SNHG1 and miR-195, whose expression vectors were constructed and then transfected into CCCs, so as to observe their effects on the cells. Western blotting (WB) was carried out to detect protein levels. MTT assay was conducted to detect cell activity. Flow cytometry was performed to detect cell apoptosis. Transwell was carried out to detect cell invasion and migration. RESULTS: The expression of lncRNA SNHG1 up-regulated while that of miR-195 down-regulated in CCCs. lncRNA SNHG1 regulated NEK2 through its targeted binding to miR-195. The down-regulation of lncRNA SNHG1 or the up-regulation of miR-195 led to the decrease of NEK2 and the reduction of cells' activity, migration and invasion, also resulting in the increase of cell apoptosis. Rescue experiments showed that the down-regulation of miR-195 could offset the cell changes caused by lncRNA SNHG1. CONCLUSION: lncRNA SNHG1 promotes the progression of cervical cancer through the miR-195/NEK2 axis, so lncRNA SNHG1, miR-195 and NEK2 may have potential values for diagnosing and treating cervical cancer.

Gephyromycin C, a novel small-molecule inhibitor of heat shock protein Hsp90, induces G2/M cell cycle arrest and apoptosis in PC3 cells in vitro.

Gephyromycin C (GC), a natural compound isolated from a marine-derived actinomycete Streptomyces sp. SS13I, which exerts anti-proliferative effect on PC3 cells. However, its underlying mechanism of the anti-cancer effect remains unknown. The results of SRB assays showed that GC inhibited the proliferation of PC3 cells with an IC50 value of 1.79 ± 0.28 µM. GC also induced G2/M cell cycle arrest which was accompanied by declining levels of cyclin proteins. Possible mechanisms were investigated and it was found that GC bound to Hsp90 and caused the degradation of Hsp90 client proteins (AKT, CHK1, P53, CDK4, Raf-b, and Raf-1). The fluorescent polarization assay with FITC-labeled geldanamycin (FITC-GA) demonstrated that GC was able to compete with FITC-GA in binding to wild type Hsp90 with an IC50 of 2.15 µM. Results of a docking study also suggested that GC interacted with the N-terminal domain of Hsp90. Our results showed that GC could bind to Hsp90, which resulted in down-regulation of Hsp90 client proteins and G2/M arrest in PC3 cells. Since the antitumor effects of this kind of angucycline via targeting Hsp90 has not been reported before, our results indicate that GC is a novel inhibitor of Hsp90 from marine resources and worthy of further study.

Lactoquinomycin C and D, two new medermycin derivatives from the marine-derived Streptomyces sp. SS17A.

Lactoquinomycin C (1) and Lactoquinomycin D (2), two new medermycin derivatives together with six known compounds (3-8) were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. SS17A. The intriguing structural features of the Lactoquinomycin D (2) which contains 5,14-epoxidation is relatively rare in medermycin derivatives. Compounds 1 and 2 exhibited no cytotoxicity against PC-3 and HCT-116 cancer cell lines, whereas compound 3 showed stronger cytotoxicity with IC50 values of 0.02 and 0.04 µM, respectively. A structure-activity relationship was observed for the cytotoxicity of the medermycin derivatives with a γ-lactone unit is required for significant cytotoxicity based on compounds 1-3.

Actin-capping protein CapG is associated with prognosis, proliferation and metastasis in human glioma.

Glioma is the most aggressive and malignant primary brain tumor in adults. In the present study, we identified a vital oncoprotein, capping actin protein, gelsolin-like (CapG), and investigated its roles in the prognosis, proliferation and metastasis in glioma. The mRNA and protein levels of CapG were significantly increased in human glioma, and higher CapG expression was an independent prognostic factor for predicting unfavorable prognosis. The expression level of CapG was found to be associated with several common molecular features of glioblastoma (GBM; WHO grade IV glioma) in The Cancer Genome Atlas (TCGA) cohort. When analyzing the prognosis of GBM patients according to these molecular features, we observed that the prognostic value of CapG was affected by amplification of CDK6 or EGFR. However, overexpression of CapG markedly promoted cell growth in vitro, while depletion of CapG significantly inhibited cell proliferation by blocking the cell cycle in G1/S transition. Moreover, CapG manipulation in glioma cell lines U87 and U251 showed CapG-dependent cellular migration and invasiveness. These data suggest that CapG may serve as a prognostic biomarker with potentially important therapeutic implications for glioma.

Cytoprotective role of nitric oxide in HepG2 cell apoptosis induced by hypocrellin B photodynamic treatment.

Hypocrellin B (HB), a natural perylenequinone pigment, has been successfully employed in the photodynamic therapy (PDT) in a variety of human cancer cells due to its high singlet oxygen yield. To investigate the generation of nitric oxide (NO) and its role on cancer cell death induced by PDT, we used human hepatocellular carcinoma (HepG2) cells and HB as a photosensitizer. HB/light treatment decreased the growth of HepG2 cells in a dose-dependent manner with an IC50 of 3.10µM, activated caspase-3, -9 and induced apoptosis in HepG2 cells. It was found that exposure of the cells to HB/light resulted in inducible nitric oxide synthase (iNOS) activation and followed by significant increase in NO generation. Incubating cells with a NOS inhibitor N(ω)-monomethyl-l-arginine (l-NMMA) and an NO scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) enhanced HB/light-induced caspase-3, -9 activation and apoptosis significantly while decreasing DAF fluorescence-assessed NO generation substantially. Cells could be rescued from HB/light-induced apoptosis by an exogenous NO donor, sodium nitroprusside (SNP). Our findings suggested that induced NO was acting cytoprotectively and PDT efficacy of HB could be improved by using pharmacological modulators of NO or NOS.

Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats.

AIM: To evaluate preventative effects of ischemic preconditioning (IP) in a rat model of intestinal injury induced by ischemia-reperfusion (IR). METHODS: Male Sprague-Dawley rats (250-300 g) were fasted for 24 h with free access to water prior to the operation. Eighteen rats were randomly divided into three experimental groups: S group (n = 6), rats were subjected to isolation of the superior mesenteric artery (SMA) for 40 min, then the abdomen was closed; IR group (n = 6), rats were subjected to clamping the SMA 40 min, and the abdomen was closed followed by a 4-h reperfusion; IP group (n = 6) rats underwent three cycles of 5 min ischemia and 5 min reperfusion, then clamping of the SMA for 40 min, then the abdomen was closed and a 4-h reperfusion followed. All animals were euthanized by barbiturate overdose (150 mg/kg pentobarbital sodium, i.v.) for tissue collection, and the SMA was isolated via median abdominal incision. Intestinal histologic injury was observed. Malondialdehyde (MDA), myeloperoxidase (MPO) and tumor necrosis factor (TNF)-α concentrations in intestinal tissue were measured. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression, as well as nuclear factor (NF)-κB activity and expression in intestinal tissue were also determined. RESULTS: Compared with the IR group, IP reduced IR-induced histologic injury of the intestine in rats (2.00 ± 0.71 vs 3.60 ± 0.84, P < 0.05). IP significantly inhibited the increase in MDA content (5.6 ± 0.15 µmol/L vs 6.84 ± 0.18 µmol/L, P < 0.01), MPO activity (0.13 ± 0.01 U/L vs 0.24 ± 0.01 U/L, P < 0.01), and TNF-α levels (7.79 ± 2.35 pg/mL vs 10.87 ± 2.48 pg/mL, P < 0.05) in the intestinal tissue of rats. IP also markedly ameliorated the increase in ICAM-1 (204.67 ± 53.27 vs 353.33 ± 45.19, P < 0.05) and VCAM-1 (256.67 ± 58.59 vs 377.33 ± 41.42, P < 0.05) protein expression in the intestinal tissues. Additionally, IP remarkably decreased NF-κB activity (0.48 ± 0.16 vs 0.76 ± 0.22, P < 0.05) and protein expression (320.23 ± 38.16 vs 520.76 ± 40.53, P < 0.01) in rat intestinal tissue. CONCLUSION: IP may protect against IR-induced intestinal injury by attenuation of the neutrophil-endothelial adhesion cascade via reducing ICAM-1 and VCAM-1 expression and TNF-α-induced NF-κB signaling pathway activity.

Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2E,6E)-2,6-bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH).

The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•- quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63-5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

The prognostic value of CXCR4 in ovarian cancer: a meta-analysis.

OBJECTIVE: Recent reports have shown that C-X-C chemokine receptor 4 (CXCR4) is expressed in ovarian cancer and plays an important role in metastasis. However, the prognostic value of CXCR4 in ovarian cancer remains controversial and has not been emphasized. The aim of this study is to evaluate the prognostic significance of CXCR4 in ovarian cancer by performing a meta-analysis. METHODS: We systematically searched for studies evaluating the relationship between CXCR4 expression and the outcome of ovarian cancer patients. Only articles in which CXCR4 expression was detected by immunohistochemical staining were included. Hazard ratios (HRs) and relative risk (RR) with 95% confidence intervals (CIs) were pooled as effect size (ES) across studies for overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 729 patients from 7 studies (6 articles) were included in this meta-analysis. Our results showed that high CXCR4 expression was significantly associated with poor prognosis in terms of OS (ES, 2.81; 95% CI, 1.16-6.80; p = 0.022) and PFS (ES, 8.48; 95% CI, 2.13-33.70; p = 0.002) in ovarian cancer patients. The association between high CXCR4 expression and poor ovarian cancer prognosis in OS was also statistically significant in subgroups of Asian and III-IV patients constituting 70%. CONCLUSIONS: The present meta-analysis indicated that high CXCR4 expression was associated with poor prognosis in ovarian cancer. More studies, especially larger scale and well-matched researches, are warranted to clarify the prognostic effect of CXCR4 on the outcome of ovarian cancer.

GS-2, a pyrazolo[1,5-a]indole derivative with inhibitory activity of topoisomerases, exerts its potent cytotoxic activity by ROS generation.

Pyrazolo[1,5-a]indole derivatives, a new type of topoisomerase (topo) inhibitor, demonstrate a broad spectrum of antitumor activities. However, the mechanism underlying the induced cytotoxicity remains unclear. In this study, we investigated whether GS-2, one of the derivatives, altered the levels of ROS in breast cancer MDA-231 cells and whether these ROS contributed to the observed antitumoral activity. Our data revealed that GS-2 caused a time- and dose-dependent elevation of intracellular ROS level in MDA-231 cells. GS-2 subsequently elicited notable inhibition on the expression of topos, DNA damage, activation of caspase-3, -9. The loss of mitochondrial membrane potential (MMP) was observed during the induction. The addition of N-acetyl cysteine (NAC, a well-known antioxidant) could effectively attenuate the GS-2-induced ROS enhancement and subsequent apoptosis. NAC attenuated the induced inhibition on expression of topos, indicating that topos might be the target of GS-2-induced ROS. The finding of the induced ROS provides new evidence for the molecular mechanisms of antitumor activity of pyrazolo[1,5-a]indole derivatives.

Interference of suppressor of cytokine signaling 3 promotes epithelial-mesenchymal transition in MHCC97H cells.

AIM: To investigate the role of suppressor of cytokine signaling 3 (SOCS3) silencing in epithelial-mesenchymal transition (EMT) involved in a human hepatocellular carcinoma MHCC97H cell line. METHODS: MHCC97H cells were transiently transfected with SOCS3 small-interfering RNA (siRNA). Morphological changes of the transfected cells were observed under microscope. Expressions of E-cadherin, Vimentin and α-smooth muscle actin (α-SMA) were identified with immunofluorescence. Furthermore, protein expressions and mRNA levels of characteristic markers of EMT (E-cadherin, Vimentin, α-SMA and Snail) were detected by Western blotting, quantitative real-time polymerase chain reaction. Transforming growth factor-ß1 (TGF-ß1) levels in the supernatant were measured with enzyme-linked immunosorbent assay. RESULTS: The transfected cells with SOCS3 siRNA showed a morphological alteration from a typical cobblestone morphology to mesenchymal spindle-shaped and fusiform features. SOCS3 siRNA lessened immunofluorescent expression of E-cadherin, but elicited immunofluorescent expressions of Vimentin and α-SMA in MHCC97H cells. More importantly, compared with the negative control, depletion of SOCS3 resulted in the decrease of the epithelial marker E-cadherin (P < 0.05), and the increase of the mesenchymal markers Vimentin and α-SMA and the transcription factor Snail in MHCC97H cells (P < 0.05). Moreover, compared with the negative control, SOCS3 siRNA evidently enhanced TGF-ß1 secretion in MHCC97H cells (200.20 ± 29.02 pg/mL vs 490.20 ± 92.43 pg/mL, P < 0.05). CONCLUSION: SOCS3 silencing is able to promote EMT in MHCC97H cells via changing the phenotypic characteristics and modulating the characteristic markers.

Effects and mechanisms of the functional parts of Dahuang Zhechong pill containing serum on platelet-derived growth factor-stimulated proliferation of vascular smooth muscle cells.

OBJECTIVE: To investigate and compare the effects and mechanisms of three functional parts of Dahuang Zhechong Pill (DHZCP), including drugs with the function of removing blood stasis and promoting blood circulation (FP-I), drugs with the function of expelling heat and moistening dryness (FP-II), and drugs with the function of nourishing yin and replenishing blood (FP-III) of DHZCP, on platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMCs) proliferation with the method of serum pharmacology. METHODS: VSMCs proliferation of rat was assayed by measuring the cell viability with the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) method. DNA synthesis in VSMCs was examined by detecting 5'-bromo-2'-deoxyuridine incorporation with the immunocytochemical method. Cycle of VSMCs was evaluated with flow cytometry. Expression of cyclin D1, p27, PKCα, and phosphorylated extracellular signal regulated kinase 1/2 (ERK1/2) was quantified by the Western blotting method. RESULTS: The FP-I and FP-III containing serum was capable of inhibiting PDGF-stimulated proliferation and DNA synthesis of VSMCs, arrested VSMCs in G phase, downregulated cyclin D1, and upregulated p27 expression (P <0.01 or P <0.05). The FP-I and FP-III containing serum also inhibited the PDGF-induced phosphorylation of tyrosine of ERK1/2 and PKCα expression (P <0.01 or P <0.05). CONCLUSIONS: FP-I and FP-III of DHZCP are able to inhibit VSMCs proliferation via interrupting PKCα-ERK1/2 signaling, modulating the expression of cell cycle proteins to result in arresting the cells in G phase. The inhibitory effect is mainly related to the function of removing blood stasis and promoting blood circulation, slightly to the function of nourishing yin and replenishing blood, but not to the function of expelling heat and moistening dryness.

Cytotoxic activities and DNA binding properties of 1-methyl-7H-indeno[1,2-b]quinolinium-7-(4-dimethylamino) benzylidene triflate.

The interaction of calf thymus DNA (ct-DNA) with a novel synthesized pyrazolo[1,5-a]indole compound 1-methyl-7H-indeno[1,2-b]quinolinium-7-(4-dimethylamino) benzylidene triflate (MIDBT) was extensively studied by various spectroscopic techniques, viscosity measurements, and gel electrophoresis. The UV-visible observation implied that the compound interacted with ct-DNA by two binding modes, intercalating into the DNA base pairs and attaching to the helix exterior of DNA. The results of the fluorescent quenching and viscosity measurements showed that MIDBT could intercalate into DNA base pairs deeply in a classical intercalative mode. Circular dichroism results showed that the binding of MIDBT shifted ct-DNA conformation from B to A at low concentrations. In the gel electrophoresis, the compound was found to promote the cleavage of plasmid pBR 322 DNA effectively. Furthermore, cytotoxic studies of this compound against eleven selected tumor cell lines have been done. The values of 50% cytotoxic concentration (IC(50)) were in the range of 1.09-18.84 µM, exhibiting the potent cytotoxic properties.