Improving the storage quality and suppressing off-flavor generation of winter jujube by precise micro-perforated MAP.

Introduction: Traditional modified atmosphere packaging (MAP) cannot meet the preservation requirements of winter jujube, and the high respiration rate characteristics of winter jujube will produce an atmosphere component with high CO2 concentration in traditional MAP. Micro-perforated MAP is suitable for the preservation of winter jujube due to its high permeability, which can effectively remove excess CO2 and supply O2. In this study, a microporous film preservation system that can be quickly applied to winter jujube was developed, namely PMP-MAP (precise micro-perforated modified atmosphere packaging). An experiment was designed to store winter jujube in PMP-MAP at 20°C and 2°C, respectively. The quality, aroma and antioxidant capacity, etc. of winter jujube at the storage time were determined. Methods: In this study, the optimal micropore area required for microporous film packaging at different temperatures is first determined. To ensure the best perforation effect, the effects of various factors on perforation efficiency were studied. The gas composition within the package was predicted using the gas prediction equation to ensure that the gas composition of the perforated package achieved the desired target. Finally, storage experiments were designed to determine the quality index of winter jujube, including firmness, total soluble solids, titratable acid, reddening, and decay incidence. In addition, sensory evaluation, aroma and antioxidant capacity were also determined. Finally, the preservation effect of PMP-MAP for winter jujube was evaluated by combining the above indicators. Results and discussion: At the end of storage, PMP-MAP reduced the respiration rate of winter jujube, which contributed to the preservation of high total soluble solids and titratable acid levels, and delayed the reddening and decay rate of winter jujube. In addition, PMP-MAP maintained the antioxidant capacity and flavor of winter jujube while inhibiting the occurrence of alcoholic fermentation and off-flavors. This can be attributed to the effective gas exchange facilitated by PMP-MAP, thereby preventing anaerobic stress and quality degradation. Therefore, the PMP-MAP approach is an efficient method for the storage of winter jujube.

Nanocarrier-based targeting of metabolic pathways for endometrial cancer: Status and future perspectives.

Cancer is the second-most lethal global disease, as per health reports, and is responsible for around 70% of deaths in low- and middle-income countries. Endometrial cancer is one of the emerging malignancies and has been predicted as a public health challenge for the future. Insulin resistance, obesity, and diabetes mellitus are the key metabolic factors that promote risks for the development of endometrial cancer. Various signaling pathways and associated genes are involved in the genesis of endometrial cancer, and any mutation or deletion in such related factors leads to the induction of endometrial cancer. The conventional way of drug delivery has been used for ages but is associated with poor management of cancer due to non-targeting of the endometrial cancer cells, low efficacy of the therapy, and toxicity issues as well. In this context, nanocarrier-based therapy for the management of endometrial cancer is an effective alternate choice that overcomes the problems associated with conventional therapy. In this review article, we highlighted the nanocarrier-based targeting of endometrial cancer, with a special focus on targeting various metabolic signaling pathways. Furthermore, the future perspectives of nanocarrier-based targeting of metabolic pathways in endometrial cancer were also underpinned. It is concluded that targeting metabolic signaling pathways in endometrial cancer via nanocarrier scaffolds is the future of pharmaceutical design for the significant management and treatment of endometrial cancer.

The effect of endocrine-disrupting chemicals on placental development.

Endocrine-disrupting chemicals (EDCs) or endocrine disruptors are substances that are either naturally occurring or artificial and are released into the natural environment. Humans are exposed to EDCs through ingestion, inhalation, and skin contact. Many everyday household items, such as plastic bottles and containers, the liners of metal food cans, detergents, flame retardants, food, gadgets, cosmetics, and pesticides, contain endocrine disruptors. Each hormone has a unique chemical makeup and structural attributes. The way that endocrine hormones connect to receptors is described as a "lock and key" mechanism, with each hormone serving as the key (lock). This mechanism is enabled by the complementary shape of receptors to their hormone, which allows the hormone to activate the receptors. EDCs are described as exogenous chemicals or compounds that have a negative impact on organisms' health by interacting with the functioning of the endocrine system. EDCs are associated with cancer, cardiovascular risk, behavioural disorders, autoimmune abnormalities, and reproductive disorders. EDCs exposure in humans is highly harmful during critical life stages. Nonetheless, the effect of EDCs on the placenta is often underestimated. The placenta is especially sensitive to EDCs due to its abundance of hormone receptors. In this review, we evaluated the most recent data on the effects of EDCs on placental development and function, including heavy metals, plasticizers, pesticides, flame retardants, UV filters and preservatives. The EDCs under evaluation have evidence from human biomonitoring and are found in nature. Additionally, this study indicates important knowledge gaps that will direct future research on the topic.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.

Methyl salicylate affects the lipophilic and hydrophilic antioxidant capacities of apricot by regulating carotenoid biosynthesis and phenolic metabolism.

The carotenoid biosynthesis and phenolic metabolism were studied to explain the effect of methyl salicylate (MeSA) on the lipophilic antioxidant capacity (LAC) and hydrophilic antioxidant capacity (HAC) in apricot during postharvest storage. Our results indicated that the HAC of apricot was higher than LAC and mainly responsible for total antioxidant capacity of apricot. Preharvest spraying of MeSA (0.2 mmol L-1) could improve the value of HAC but declined LAC of apricot. The enhanced HAC in MeSA treated apricot was positively related to the increased content of phenolics, especially to (+)-catechin, which was catalyzed by the enzymes related to phenolic metabolism. While, the decline of LAC in apricot treated by MeSA could be attributed to the inhibition of carotenoids accumulation, which was regulated by carotenogenic genes. We concluded that MeSA could affect the lipophilic and hydrophilic antioxidant capacity of apricot by regulating carotenoid biosynthesis and phenolic metabolism.

[Retracted] Downregulation of matrix metalloproteinase 9 by small interfering RNA inhibits the tumor growth of ovarian epithelial carcinoma in vitro and in vivo.

Following the publication of this paper, the authors contacted the Editorial Office to request that the article be retracted on account of an inability to obtain consistent results after having repeated the experiments portrayed in Figs. 1B and 3B. Independently, it was drawn to the Editor's attention that certain of the western blotting data shown in these figures were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that these other articles were under consideration for publication at the same time as the above article was submitted for publication to Molecular Medicine Reports, the Editor has agreed to the authors' request that this article should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 753­759, 2015; DOI: 10.3892/mmr.2015.3425].

[Retracted] Effects of cyclooxygenase­2 gene silencing on the biological behavior of SKOV3 ovarian cancer cells.

Following the publication of the above article, the authors have requested that it be retracted. They alerted the Editorial Office to the fact that the same data, albeit with a different view, had been selected to show the 'CON' and 'NC' experiments for the colony­formation assays featured in Fig. 6. The Editor has agreed to the authors' request that the paper be retracted. All the authors agree to this retraction, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 11: 59­66, 2015; DOI: 10.3892/mmr.2014.2732].

PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells.

Although the biomedical sciences have achieved tremendous success in developing novel approaches to managing prostate cancer, this disease remains one of the major health concerns among men worldwide. Liposomal formulations of single drugs have shown promising results in cancer treatment; however, the use of multi drugs has shown a better therapeutic index than individual drugs. The identification of cancer-specific receptors has added value to design targeted drug delivering nanocarriers. We have developed genistein and plumbagin co-encapsulating liposomes (∼120 nm) with PSMA specific antibodies to target prostate cancer cells selectively in this work. These liposomes showed >90 % decrease in PSMA expressing prostate cancer cell proliferation without any appreciable toxicity to healthy cells and human red blood cells. Release of plumbagin and genistein was found to decrease the expression of PI3/AKT3 signaling proteins and Glut-1 receptors (inhibited glucose uptake and metabolism), respectively. The decrease in migration potential of cells and induced apoptosis established the observed anti-proliferative effect in prostate cancer cell lines. The discussed strategy of developing novel, non-toxic, and PSMA specific antibody conjugated liposomes carrying genistein and plumbagin drugs may also be used for encapsulating other drugs and inhibit the growth of different types of cancers.

A novel GPCR target in correlation with androgen deprivation therapy for prostate cancer drug discovery.

Most prostate carcinomas require androgen stimulation to grow, and for nearly 70 years, androgen ablation therapy has been one of the central therapeutic strategies against advanced prostate cancer. Although most tumours initially respond to this therapy, some will be acquired resistant and progress to metastatic castration-resistant (mCRPC) disease which clinically tends to progress more rapidly than earlier disease manifestations. The underlying molecular biology of mCRPC is highly complex, and numerous mechanisms have been proposed that promote and retain androgen independence. In various clinical and preclinical data explored, the nature of intracellular signalling pathways mediating mitogenic acquired resistant effects of GPCRs in prostate cancer is poorly defined. G-protein-coupled receptor kinase 2 (GRK2) contributes to the modulation of basic cellular functions-such as cell proliferation, survival or motility-and is involved in metabolic homeostasis, inflammation or angiogenic processes. Moreover, altered GRK2 levels are starting to be reported in different tumoural contexts and shown to promote breast tumourigenesis or to trigger the tumoural angiogenic switch. Thus, we are exploring recent findings that present unexpected opportunities to interfere with major tumourigenic signals by manipulating GPCR-mediated pathways.

Laboratory Investigation of Aging Resistance for Rubberized Bitumen Modified by Using Microwave Activation Crumb Rubber and Different Modifiers.

Different modification methods, such as adding modifiers and pretreating crumb rubber, have been developed to achieve decent engineering properties and reduce the viscosity of rubberized bitumen. This study evaluated the influence of the modification methods on the aging resistance for rubberized bitumen. Two types of crumb rubber-a 40-mesh crumb rubber and a microwave-pretreated crumb rubber-and two kinds of modifiers-Sasobit and Trans-polyoctenamer-were selected to prepare rubberized bitumen. The samples were subjected to a Thin-Film Oven Test for the simulation of the short-term aging condition, while a Pressure-Aging-Vessel test was used to simulate the long-term aging condition. The indexes of rubberized bitumen, including softening point, elastic recovery ratio, maximum load, ductility, fracture energy, phase angle, and dynamic modulus, were tested before and after aging. The result showed that trans-polyoctenamer displayed the best resistance to short-term aging, while Sasobit significantly improved the fracture energy of rubberized bitumen after short-term aging. Microwave pretreated partially destroyed the internal structure of crumb rubber, leading to a decrease of short-term aging resistance for rubberized bitumen. Compared with short-term aging, the changing trends of various indexes were basically same, except the discrepancy of properties indexes was reduced after long-term aging.

A novel inhibitory role of microRNA-224 in particulate matter 2.5-induced asthmatic mice by inhibiting TLR2.

Epidemiological studies have shown that elevated concentrations of particulate matter 2.5 (PM2.5) correlate with increased incidence of asthma. Studies have highlighted the implication of microRNAs (miRNAs) in asthmatic response. Here, the objective of this study is to explore the effect of miR-224 on PM2.5-induced asthmatic mice. Ovalbumin (OVA) was utilized to establish asthmatic mouse models, which were then exposed to PM2.5, followed by miR-224 expression detection. Next, lesions and collagen deposition area in lung tissue, ratio Treg/Th17, the expression of TLR4 and MYD88, inflammation, eosinophils (EOS) and airway remodelling were evaluated in OVA mice after injection with miR-224 agomir. Following isolation of mouse primary bronchial epithelial cells, miR-224 mimic and TLR2/TLR4 inhibitor were introduced to assess inflammation and the expression of TGF-ß, MMP9, TIMP-1, Foxp3, RORγt, TLR2, TLR4 and MYD88. After exposure to PM2.5, lesions and collagen deposition were promoted in lung tissues, inflammation and EOS were increased in bronchoalveolar lavage fluid (BALF), and airway remodelling was enhanced in OVA mice. miR-224 was down-regulated, whereas TLR2/TLR4/MYD88 was up-regulated in OVA mice after treatment with PM2.5, accompanied by Treg/Th17 immune imbalance. Of note, bioinformatic prediction and dual luciferase reporter gene assay confirmed that TLR2 was a target gene of miR-224. Overexpressed miR-224 reduced expression of TGF-ß, MMP9, TIMP-1 and RORγt and inflammation but increased Foxp3 expression in bronchial epithelial cells through down-regulating TLR2. In summary, overexpressed miR-224 suppressed airway epithelial cell inflammation and airway remodelling in PM2.5-induced asthmatic mice through decreasing TLR2 expression.

Dehydrofreezing of peach: Blanching, D-sodium erythorbate vacuum infiltration, vacuum dehydration, and nitrogen packaging affect the thawed quality of peach.

Peach slices were blanched (BL), vacuum infiltrated with D-sodium erythorbate (SE), predehydrated, and then nitrogen packaged (NP) before freezing to improve their quality. Our results showed that the BL, SE, and NP pretreatments remarkably improved the quality of frozen peaches. Frozen peaches pretreated by SE+NP+BL showed the highest total phenolic content (TPC), total antioxidant capacity (TAC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity after thawing at 20°C for 24 hr. The soluble solids content and firmness of low-maturity peaches dehydrated to 25% dehydration of their weight were 11.1% and 211.2% higher than those of the control samples, respectively, while their drip loss was 71.9% lower than that of the controls. In conclusion, pretreatment by BL, predehydration, SE, and NP before freezing can significantly improve the quality of frozen peaches after thawing. PRACTICAL APPLICATIONS: We believe that our study results have practical applications because the method of vacuum dehydration combined with blanching, nitrogen packaging, and D-sodium erythorbate treatment of peaches maintains their original taste, inhibits color change, and decreases drip loss. This method is suitable for fruit frozen and stored at a commercial freezing temperature of -20°C and does not need advanced equipment or technology. It can be easily carried out during the fruit freezing process and can be applied to other frozen stored fruits besides peaches.

Cell wall polysaccharides degradation and ultrastructure modification of apricot during storage at a near freezing temperature.

The effects of near freezing temperature (NFT) storage at -1.9 °C on cell wall degradation of 'Shushanggan' apricot was studied comparing to 0 °C and 5 °C storage. Our results indicated that NFT storage strongly inhibited the solubilization of Na2CO3-soluble pectin and cellulose, by the suppression of cell wall modifying enzymes (polygalacturonase, ß-Galactosidase, pectin methyl esterase and cellulase) and related genes expressions. The loss of side chains was the main modification in CDTA (Cyclohexane-diamine-tetraacetic Acid)-soluble pectin during storage and made the main contribution to the softening of apricot, while the loss of side chain was suppressed by NFT storage. Microscopic observation showed that NFT storage delayed the degradation of pectin fraction and protected cell wall structure from loosing. This study proves that NFT storage is an effective technology to suppress the cell wall polysaccharides degradation and ultrastructure modification of apricot.

Impaired Th17 cell proliferation and decreased pro-inflammatory cytokine production in CXCR3/CXCR4 double-deficient mice of vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is a common observed infection, affecting approximately 75% of women of reproductive age. Drug resistance represents a troublesome stumbling block associated with VVC therapy. Thus the aim of the present study was to provide information regarding the selection of potential drug targets for VVC. CXCR3-, CXCR4-, or CXCR/CXCR4 double-deficient mouse models of VVC were subsequently established, with changes to the load of Candida Albicans evaluated accordingly. The biological behaviors of the vaginal epithelial cells were characterized in response to the CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout in vivo. Our initial observations revealed that in mice with VVC, CXCR3-, CXCR4-, or CXCR3 - CXCR4 double-knockout resulted in a decreased load of C. Albicans as well as reduced levels and proportion of Th17 cells. Proinflammatory cytokine production was found to be inhibited by CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout whereby the mRNA and protein expressions CXCR3, CXCR4, IL-17, IL-6, and TNF-α exhibited decreased levels. CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout appeared to function as positive proliferation factors, while playing a negative role in the processes of apoptosis and the cell cycle of vaginal epithelial cells. Taken together, the key findings of the study suggested that CXCR3/CXCR4 double-knockout could act to hinder the progression of VVC, highlighting its promise as a novel therapeutic target in the treatment of VVC. CXCR3 and CXCR4 genes may regulate Th17/IL-17 immune inflammatory pathways to participate in antifungal immunity.

Nanoliposomal formulation encapsulating celecoxib and genistein inhibiting COX-2 pathway and Glut-1 receptors to prevent prostate cancer cell proliferation.

Globally, prostate cancer remains a challenging health burden for men as it is the second leading cause of cancer death in men and about one in nine will be diagnosed with prostate cancer in his lifetime. Enhanced expression of COX-2 and Glut-1 proteins are reported as major factors leading to the origin and progress of prostate cancer through modulating the associated signaling pathways. In this study, we have synthesized a multifunctional liposomal system containing celecoxib and genistein drugs. The combinatorial effect of these drugs leads to the selectively induce the apoptosis of prostate cancer cells than normal fibroblast cells. The mechanistic study suggests that enhanced reactive oxygen species (ROS) formation and a decrease in cellular GSH concentration, along with inhibition of COX-2 synthesis and Glut-1 receptors are the key processes behind the inhibition of prostate cancer cells. Overall, these results provide strong evidence for the role of COX-2 and Glut-1 proteins for the progression of prostate cancer and highlighting the potential of celecoxib and genistein as a useful and combinatorial pharmacological agent for chemotherapeutic purposes in prostate cancer.

Chemoresistance and targeting of growth factors/cytokines signalling pathways: towards the development of effective therapeutic strategy for endometrial cancer.

Endometrial cancer tends to be an aggressive malignancy. Although the disease prognosis can be good at the early stages of disease, the advanced condition is not curable. Chemotherapy regimens and hormone-based therapy in combination with surgery are major approaches for the management of endometrial cancers. However, intrinsic chemoresistance reduces the success rate and increases the possibility of disease relapse. Investigation of underlying mechanisms revealed altered activation of PI3K/AKT, MAPK, fibroblast growth factor (FGF), mTOR and WNT pathways and reduced gene expression of tumor suppressor p53 in recurrent endometrial cancer. A PTEN mutation, deletion or degradation induces positive p-AKT expression, while PI3K knock-down increases the level of pro-apoptotic proteins and decreases the level of anti-apoptotic ones in cancerous cells. Additionally, RAS proteins trigger both the RAF-MEK-ERK and PI3K-PTEN-AKT signalling mechanisms, thus conferring resistance to anti-tumor agents. FGF up-regulates angiogenesis via receptor-mediated tyrosine kinase activation. Single nucleotide polymorphism, gene amplification or missense mutations of FGFR2 are associated with endometrial cancer. The mTOR complex integrates the nutrient and mitogen signals via AMPKs, S6 kinase 1 (S6K1) and eukaryotic initiation factors, causing unrestricted endometrial cellular proliferation. WNT signalling molecules, such as frizzled receptors, ß-catenin, PORCN, RSPO3 and DKK1 undergo dysregulation, and drugs targeting these pathways are under clinical trials in patients with endometrial cancer. Common therapies for endometrial tumor include platinum-based anti-neoplastics, taxanes, nucleoside analogues, immune modulators, FGFR and tyrosine kinase inhibitors, small-molecule mTOR inhibitors and drugs that trigger cell cycle arrest in the G1 phase. Taken together, the current review elucidates the mechanism underlying endometrial cancer, existing therapies and chemoresistance, and points towards the need for novel therapeutics that may promote disease-free survival.

Prostate cancer: updates on current strategies for screening, diagnosis and clinical implications of treatment modalities.

Prostate cancer is the most common cancer in men by way of diagnosis and a leading cause of cancer-related deaths. Early detection and intervention remains key to its optimum clinical management. This review provides the most updated information on the recent methods of prostate cancer screening, imaging and treatment modalities. Wherever possible, clinical trial data has been supplemented to provide a comprehensive overview of current prostate cancer research and development. Considering the recent success of immunotherapy in prostate cancer, we discuss cell, DNA and viruses based, as well as combinatorial immunotherapeutic strategies in detail. Furthermore, the potential of nanotechnology is increasingly being realized, especially in prostate cancer research, and we provide an overview of nanotechnology-based strategies, with special emphasis on nanotheranostics and multifunctional nanoconstructs. Understanding these recent developments is critical to the design of future therapeutic strategies to counter prostate cancer.

Phosphorylation of STAT3 at Tyr705 regulates MMP-9 production in epithelial ovarian cancer.

Ovarian cancer's poor progression is closely associated with overexpression of matrix metalloproteinase 9 (MMP-9), which belongs to the class of enzymes believed to be involved in the degradation of extracellular matrix. However, the mechanisms underlying regulation of MMP-9 are not completely understood. STAT (signal transducer and activator of transcription) family of transcription factors is well known to be engaged in diverse cellular functions. Activation of STAT3 has been observed in a number of cancers, promoting tumorigenesis and metastasis via transcriptional activation of its target genes. In this study, we tested our hypothesis that STAT3 regulates MMP-9 gene expression in epithelial ovarian cancer. Using epithelial ovarian cancer cell lines as in vitro model, we show an abundance of phosphorylated STAT3 at Tyr705 (p-STAT3) in SKOV3 cell line. We further show that MMP-9 gene promoter was significantly enriched by p-STAT3, and IL-6 treatment led to a significant increase of MMP-9 at mRNA and protein levels, in addition to an association of p-STAT3 with MMP-9 gene. By using luciferase reporter assay, we determined that the STAT3 DNA responsive element of MMP-9 was sufficient to regulate transcriptional activity of a heterologous promoter. These results suggest that the phosphorylation of STAT3 regulates MMP-9 production in ovarian cancer, which might be responsible for its invasiveness and metastasis.

Antithrombotic activity of oral administered low molecular weight fucoidan from Laminaria Japonica.

INTRODUCTION: Fucoidans extracted from brown algae have been documented to have excellent antithrombotic activity when administered by either intravenous or subcutaneous route in animal models. However, it is unknown if the fucoidans also have antithrombotic activity when administered orally, a highly desirable feature of oral antithrombotic agents. In the present study, we compared the oral absorption, bioavailability and antithrombotic activity of two fucoidan fractions from Laminaria japonica with different molecular weight by oral administration in an electricity induced arterial thrombosis model and the underlying molecular mechanisms. RESULTS AND CONCLUSIONS: After a single dose of oral administration, the fucoidan content in plasma and urine in rats was assessed using the reverse-phased HPLC analysis of 1-phenyl-3-methyl-5-pyrazolone (PMP)-labeled fucose. The fucose content in the low molecular weight (LMW) fucoidan-treated rats increased up to 2-fold and peaked at 15h, indicating that the LMW fucoidan had much better absorption and bioavailability than the MMW fucoidan in vivo. Oral administration of the LMW fucoidan at 400 and 800mg/kg for 30days inhibited the arterial thrombosis formation effectively induced by electrical shock in rats, accompanied by moderate anticoagulation activity, regulation on TXB2 and 6-keto-PGF1α, significant antiplatelet activity and effective fibrinolysis. The LMW fucoidan showed better oral absorption and antithrombotic activity in addition to different antithrombotic mechanisms compared to those of the medium molecular weight (MMW) fucoidan. Thus, the LMW fucoidan has a potential to become an oral antithrombotic agent.

Downregulation of matrix metalloproteinase 9 by small interfering RNA inhibits the tumor growth of ovarian epithelial carcinoma in vitro and in vivo.

Matrix metalloproteinase 9 (MMP-9) is upregulated in various types of malignancy, including human ovarian carcinomas. It promotes invasion, metastasis, growth and the survival of malignant cells. However, relatively little is known about the role of MMP9 in epithelial ovarian carcinoma. Therefore, the aim of the present study was to determine the effects of targeting this molecule on ovarian carcinoma progression. A plasmid, psi-MMP-9, carrying a short hairpin RNA against MMP-9 gene expression was constructed and transfected into the human ovarian cancer cell line SKOV3 using a human U6 promoter-driven DNA template approach to determine the effect of MMP-9 gene RNA interference (RNAi) on the proliferation, apoptosis, migration, invasion and tumorigenicity of the human ovarian carcinoma cells. The results demonstrated that siRNA-mediated knockdown of MMP-9 in the human ovarian cancer cell line SKOV3 inhibited cell proliferation, migration and invasion in vitro. The results also demonstrated that downregulation of MMP-9 led to cell apoptosis in SKOV3 cells, inhibited the expression of anti-apoptotic molecules, including B cell lymphoma-2, survivin and X-linked inhibitor of apoptosis protein, and enhanced the activity of capsase-3 and caspase-8. In addition, knockdown of MMP-9 inhibited tumorigenicity in nude mice. Taken together, MMP-9 gene RNAi in ovarian carcinoma cells inhibited proliferation, migration and invasion, induced cell apoptosis in vitro and suppressed tumor growth in nude mice. These results suggest that MMP-9 is an ovarian cancer-associated gene and is a potential target for therapeutic anti-cancer drugs.