Near-Infrared II Hemicyanine Dye with Large Stokes Shift Designed by TICT Regulation for Boosting Imaging-Guided Photothermal Therapy.

The serious threat that cancer poses to human health highlights the significance of early detection and effective treatment. The integration of fluorescence diagnosis and photothermal therapy in NIR-II has gained attention due to its high sensitivity, fast response, and noninvasiveness. Fluorescence, produced by the radiative relaxation process of electrons in a molecule, and photothermal, generated by the nonradiative relaxation process of electrons in a molecule, are competing photophysical processes. Hence, it is a challenge for the molecule to balance between the properties of fluorescence and photothermal. In this study, a NIR-II hemicyanine with TICT character is designed to obtain molecules with both better fluorescence and photothermal properties, utilizing positively charged pyridine salt and triphenylamine as electron acceptor and donor, respectively, and oxole as the conjugated π-bridge. HCY-995, one of the synthesized compounds, has a quantum yield of 0.09%, photothermal conversion efficiency of 54.90%, and a significant Stoke shift of 232 nm, which makes it appropriate for the integration of photothermal therapy and high-resolution imaging. This study provides new insights into the development of NIR-II molecules with fluorescent and photothermal integrated properties.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses.

Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8+ T and CD49b+ NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3+ Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.

Naringenin suppresses epithelial ovarian cancer by inhibiting proliferation and modulating gut microbiota.

BACKGROUND: Ovarian cancer has the highest mortality among all gynecological malignancies; currently, no effective therapeutics are available for its treatment. Naringenin has been shown to inhibit the progression of various cancers, but its inhibitory effect on ovarian cancer remains unknown. PURPOSE: This study aimed to evaluate the inhibitory effects of naringenin on ovarian cancer and elucidate the underlying mechanisms. METHODS: Cancer cell proliferation was detected by cell counting kit-8 and crystal violet assays, and the migration capability was determined by wound healing and transwell assays. Western blotting and immunohistochemistry assays were employed to determine the expression levels of the epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3K) and cyclin D1 in vitro and in vivo, respectively. An ES-2 xenograft nude mouse model was established for the in vivo experiments, and fecal samples were collected for intestinal microbiota analysis by 16S rDNA sequencing. RESULTS: Naringenin suppressed the proliferation and migration of A2780 and ES-2 cancer cell lines and downregulated PI3K in vitro. In animal experiments, naringenin treatment significantly decreased the tumor weight and volume, and oral administration exhibited greater effects than intraperitoneal injection. Additionally, naringenin treatment ameliorated the population composition of the microbiota in animals with ovarian cancer and significantly increased the abundances of Alistipes and Lactobacillus. CONCLUSION: Naringenin suppresses epithelial ovarian cancer by inhibiting PI3K pathway expression and ameliorating the gut microbiota, and the oral route is more effective than parenteral administration.

Pharmacological Effects of Natural Components Against Ovarian Cancer and Mechanisms.

Ovarian cancer, one of the three leading malignancies in women, has high incidence and mortality worldwide. It is hard to diagnose until very late stages and the 5-year survival rate is very low, due mostly to its distant metastasis. Chemotherapy is currently the most common treatment to inhibit cancer growth, but long-term use could result in resistance and tumor recurrence in addition to damages to normal tissues and functions of the patients. In order to achieve safe and curative effects against cancers, many investigators have focused their attention on traditional Chinese herbal medicines. Paclitaxel, a natural antitumor agent, has significant effects on advanced malignancies including ovarian cancer and is in the standard front-line treatment. Additional natural anticancer substances have continually been discovered for their high effectiveness and low side-effects in ovarian cancer prevention and therapy. In this chapter, we summarize recent work on a selected group of natural components, including lignans, ellagic acid, luteolin, mangiferin, and Acanthopanax senticosus, which have all been demonstrated to reduce the progress of epithelial ovarian cancer in a dose-depend manner, by both in vitro and in vivo experiments. The mechanisms of the anticancer activities by these natural components involve expression suppression of MMP2 and MMP9.

Suppressive activities of mangiferin on human epithelial ovarian cancer.

BACKGROUND: Epithelial carcinoma is a subtype of ovarian cancers, with the highest lethality among all ovarian cancer subtypes. Hitherto surgical excision combined with chemotherapy has been the most extensively employed method in clinical treatment. However, the disease relapses very frequently, calling for more effective therapies. Mangiferin, a natural xanthone glucoside, has displayed promising anti-cancer activities by in vitro studies, but its therapeutic value in epithelial ovarian cancer treatment, either by in vivo or in vitro studies, remained to be known. PURPOSE: This study aimed to determine the suppressive activities of mangiferin on human epithelial ovarian cancer and elucidate the underlying molecular mechanisms. STUDY DESIGN AND METHODS: We employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the crystal violet assay to determine the half maximal inhibitory concentration (IC50) values of mangiferin with paclitaxel as a positive control and the inhibitory effects of mangiferin on the proliferation of two human epithelial ovarian cancer cell lines. Wound healing and Transwell assays were used to determine anti-metastastic activities of mangiferin. ES-2 xenograft nude mouse model was used for the in vivo experiments. Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assays were carried out for evaluating the expression level of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). RESULTS: In the present study, we demonstrated by both in vitro and in vivo assays that mangiferin suppressed the progress of epithelial ovarian cancer in a dose-dependent manner. In the animals treated with mangiferin, the tumor volume and weight were reduced significantly. Analyses of involved molecular events demonstrated that mangiferin down-regulated the expression of metastasis-associated proteins MMP2 and MMP9. CONCLUSION: Mangiferin strongly inhibited the progression of human epithelial ovarian cancer by down-regulating MMP2 and MMP9.

Enterolactone has stronger effects than enterodiol on ovarian cancer.

BACKGROUND: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. METHODS: We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. RESULTS: The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. CONCLUSION: END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.

Acanthopanax senticosus: Photochemistry and Anticancer Potential.

Acanthopanax senticosus (previously classified as Eleutherococcus senticosus), commonly known as Ciwujia or Siberian Ginseng, is a traditional Chinese medicine (TCM), widely used for its high medicinal value, such as antifatigue, anti-inflammation, antistress, anti-ulcer and cardiovascular functions, in China, Korea, Japan and Russia. In the past decades, researchers worldwide have conducted systematic investigations on this herb, from chemistry to pharmacology, and a large number of chemical components have been characterized for their significant pharmacological effects. However, reports about the anticancer effects of this plant had been rare until recently, when considerable pharmacological experiments both in vitro and in vivo were conducted to study the anticancer effects of this herb. A. senticosus has been found to have inhibitory effects on malignant tumors, such as those in the lung and liver, suggesting that A. senticosus has potential to be developed as an effective anticancer drug. This paper reviews recent findings on the pharmacological properties of A. senticosus, with a focus on its anticancer effects.

Optimization of ultrasound extraction of Alisma orientalis polysaccharides by response surface methodology and their antioxidant activities.

Rhizoma alismatis (the rhizome of Alisma orientalis) polysaccharides (RAP) have been reported to have a variety of important biological activities. However, effective extraction of RAP has been an unsolved issue. In this study, we used an ultrasound method for high yield extraction of RAP and optimized the conditions using the response surface methodology (RSM). Following multiple regression analyses of the experimental results, we applied the 3-D response surface and the contour plots to determine the optimal conditions, which were found to be ultrasound treatment at 76.1°C for 75.2 min, and water to material ratio at 30.1 ml/g. Under such conditions, the yield was 6.90% which was much higher than traditional hot water extraction yield (3.41%). The fractionated RAPs following stepwise ethanol precipitation showed strong antioxidant activities. The results indicated that ultrasound extraction was a very effective method for the extraction of RAP and the polysaccharides could be explored as a potential antioxidant agent for use in medicine or functional food.

[Study on sustainable development of industy of ethnic medicine in minority area].

Ethnic medicine industry is facing many problems such as narrow market, exhaustion of resource, decline of ethnic medicine and no qualified successors. Sustainable development theory was utilized to analyse the elements and problems of ethnic medicine industry, and the counter measures were put forward to get rid of the predicament and to realize the sustainable development which depends on the ethnic medicine resources, national medicine, industrial policy, personnel training and modern technology. The development issues of ethnic medicine industry can be solved by the coordination of enterprise, government and public. Finally the ethnic medicine can provide better services for society.

The antidepressant effect of secoisolariciresinol, a lignan-type phytoestrogen constituent of flaxseed, on ovariectomized mice.

Secoisolariciresinol (SECO) is a natural lignan-type phytoestrogen constituent mainly found in flaxseed. It can be metabolized in vivo to mammalian lignans of enterodiol and enterolactone, which have been proven to be effective in relieving menopausal syndrome. Depression is one of the most common symptoms of menopausal syndrome, and is currently treated with estrogen replacement and antidepressant therapy. However, due to the serious side-effects of such agents, there are urgent needs for safer and more tolerable treatments. In this paper, using two classical depression models, the forced swimming test and the tail suspension test, we report the antidepressant effect of SECO on ovariectomized (OVX) mice by intragastric administration for 14 consecutive days at doses of 5, 10 and 20 mg/kg. The results showed that SECO (10 mg/kg) treatment could significantly reduce the duration of immobility of OVX mice in these two models compared with the control group (OVX mice + vehicle), which was similar to the positive control imipramine. In addition, SECO treatment could substantially increase brain monoamine (norepinephrine and dopamine) levels in OVX mice. The present studies showed that SECO can reverse depressive-like behavior and exhibit monoamine-enhancing effects.

A novel inhibitory effect of Antrodia camphorata extract on vascular smooth muscle cell migration and neointima formation in mice.

Antrodia camphorata (AC) is a well-known traditional Chinese medicine that has been shown to inhibit proliferation and migration of cancer cells. We examined whether AC could inhibit rat aortic smooth muscle cell (RASMC) proliferation and migration and evaluated its effect on neointima formation in mouse carotid artery after injury. In Transwell migration assay and wound scratch assay, RASMCs were treated with AC or saline, and the number of migrated cells was counted or the distance was determined. Both assays showed that AC significantly inhibited platelet-derived growth factor (PDGF)-induced SMC migration. In 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and 5-bromo-2' deoxyuridine (BrdU) proliferation assays, RASMCs were pretreated with AC or saline and stimulated with PDGF. Both assays showed that AC inhibited PDGF-induced SMC proliferation. The left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation. The mice were given water or AC for 4 weeks. The severity of neointima formation was expressed as the neointima/media (N/M) ratio. The AC-treated mice had less neointima formation at 4 weeks after carotid ligation (N/M ratio, water versus 250 versus 1250 mg/kg AC; 1.33 +/- 0.87 versus 0.83 +/- 0.45 versus 0.63 +/- 0.32, P < 0.05).Our data indicate that AC is an effective inhibitor of PDGF-induced RASMC proliferation and migration. AC treatment reduced neointima formation in this mouse carotid ligation model.