Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Progress of research into the pharmacological effect and clinical application of the traditional Chinese medicine Rehmanniae Radix.

The traditional Chinese medicine (TCM) Rehmanniae Radix (RR) refers to the fresh or dried root tuber of the plant Rehmannia glutinosa Libosch of the family Scrophulariaceae. As a traditional Chinese herbal medicine (CHM), it possesses multiple effects, including analgesia, sedation, anti-inflammation, antioxidation, anti-tumor, immunomodulation, cardiovascular and cerebrovascular regulation, and nerve damage repair, and it has been widely used in clinical practice. In recent years, scientists have extensively studied the active components and pharmacological effects of RR. Active ingredients mainly include iridoid glycosides (such as catalpol and aucuboside), phenylpropanoid glycosides (such as acteoside), other saccharides, and unsaturated fatty acids. In addition, the Chinese patent medicine (CPM) and Chinese decoction related to RR have also become major research subjects for TCM practitioners; one example is the Bolus of Six Drugs, which includes Rehmannia, Lily Bulb and Rehmannia Decoction, and Siwu Decoction. This article reviews recent literature on RR; summarizes the studies on its chemical constituents, pharmacological effects, and clinical applications; and analyzes the progress and limitations of current investigations to provide reference for further exploration and development of RR.

Targeting HSP90 with picropodophyllin suppresses gastric cancer tumorigenesis by disrupting the association of HSP90 and AKT.

Gastric cancer (GC) is one of the most common malignant tumors worldwide. Thus, the development of safe and effective therapeutic compounds for GC treatment is urgently required. Here, we aimed to examine the role of picropodophyllin (PPP), a compound extracted from the rhizome of Dysosma versipellis (Hance) M. Cheng ex Ying, on the proliferation of GC cells. Our study revealed that PPP inhibits the proliferation of GC cells in a dose-dependent manner by inducing apoptosis. Moreover, our study elucidated that PPP suppresses the growth of GC tumor xenografts with no side effects of observable toxicity. Mechanistically, PPP exerts its effects by blocking the AKT/mammalian target of rapamycin (mTOR) signaling pathway; these effects are markedly abrogated by the overexpression of constitutively active AKT. Furthermore, drug affinity responsive target stability (DARTS) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) revealed that heat shock protein 90 (HSP90) may be a potential target of PPP. Surface plasmon resonance and immunoprecipitation assay validated that PPP directly targets HSP90 and disrupts the binding of HSP90 to AKT, thereby suppressing GC cell proliferation. Thus, our study revealed that PPP may be a promising therapeutic compound for GC treatment.

Phytochemical content and antioxidant activity of different anatomical parts of Corchorus olitorius and C. capsularis during different phenological stages.

Different parts of Corchorus olitorius and C. capsularis possess different antioxidant compounds. This study investigated the phytochemical components and antioxidant capacities of ultrasound-assisted extraction of different plant parts of both species using spectrophotometry at various phenological stages. Results also indicate that leaves, stems and roots of C. olitorius at various growth stages showed higher phytochemical components and antioxidant potential compared to C. capsularis. The phytochemical components from roots to leaves in C. olitorius including total polyphenol 0.97-11.11 mg GAE/g DW, total flavonoid 0.99-7.78 mg QE/g DW and total tannin 4.02-26.89 TA E/g DW, whereas C. capsularis total polyphenol 1.04-7.93 mg GAE/g DW, total flavonoid 0.77-5.5.92 mg QE/g DW and total tannin content 3.17-22.73 TA E/g DW. C. olitorius produced overall 22.23%, 13.61%, 12.24% higher total polyphenol, total flavonoid and total tannin, respectively compare to C. capsularis. Different parts extract also significantly affected antioxidant capacities including DPPH, ABTS, and FRAP activity with values of 22.03-79.46% inhibition, 10.84-104.10 µmol TE/g DW, and 10.84-104.10 µmol Fe2+/g DW respectively for C. olitorius, while C. capsularis demonstrated 14.03-70.97% of DPPH inhibition, 9.16-95.60 µmol TE/g DW of ABTS and 5.31-71.82 µmol Fe2+/g DW of FRAP activity. Moreover, leaves of the flowering stage, young stems and aged roots of both species displayed a higher content of phytochemical and antioxidant activities than other growth stages. A positive correlation between the phytochemical and antioxidant potential indicated that phenolic constituents solely affected antioxidant activity. Thus, this study established that the plant's parts and phenological growth stages significantly influence the concentration of phytoconstituents and antioxidant activities, and determine the harvesting stages of the different organs of C. olitorius and C. capsularis for considerable medicinal importance as folk and industry.

Advances in the biosynthesis and metabolic engineering of rare ginsenosides.

Rare ginsenosides are the deglycosylated secondary metabolic derivatives of major ginsenosides, and they are more readily absorbed into the bloodstream and function as active substances. The traditional preparation methods hindered the potential application of these effective components. The continuous elucidation of ginsenoside biosynthesis pathways has rendered the production of rare ginsenosides using synthetic biology techniques effective for their large-scale production. Previously, only the progress in the biosynthesis and biotechnological production of major ginsenosides was highlighted. In this review, we summarized the recent advances in the identification of key enzymes involved in the biosynthetic pathways of rare ginsenosides, especially the glycosyltransferases (GTs). Then the construction of microbial chassis for the production of rare ginsenosides, mainly in Saccharomyces cerevisiae, was presented. In the future, discovery of more GTs and improving their catalytic efficiencies are essential for the metabolic engineering of rare ginsenosides. This review will give more clues and be helpful for the characterization of the biosynthesis and metabolic engineering of rare ginsenosides. KEY POINTS: • The key enzymes involved in the biosynthetic pathways of rare ginsenosides are summarized. • The recent progress in metabolic engineering of rare ginsenosides is presented. • The discovery of glycosyltransferases is essential for the microbial production of rare ginsenosides in the future.

Therapeutic effects on cancer of the active ingredients in rhizoma paridis.

Cancer is a major threat to human health, with high mortality and a low cure rate, continuously challenging public health worldwide. Extensive clinical application of traditional Chinese medicine (TCM) for patients with poor outcomes of radiotherapy and chemotherapy provides a new direction in anticancer therapy. Anticancer mechanisms of the active ingredients in TCM have also been extensively studied in the medical field. As a type of TCM against cancer, Rhizoma Paridis (Chinese name: Chonglou) has important antitumor effects in clinical application. The main active ingredients of Rhizoma Paridis (e.g., total saponins, polyphyllin I, polyphyllin II, polyphyllin VI, and polyphyllin VII) have shown strong antitumor activities in various cancers, such as breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma (HCC), and gastric cancer. Rhizoma Paridis also has low concentrations of certain other active ingredients with antitumor effects, such as saponins polyphyllin E, polyphyllin H, Paris polyphylla-22, gracillin, and formosanin-C. Many researchers have studied the anticancer mechanism of Rhizoma Paridis and its active ingredients. This review article describes research progress regarding the molecular mechanism and antitumor effects of the active ingredients in Rhizoma Paridis, suggesting that various active ingredients in Rhizoma Paridis may be potentially therapeutic against cancer.

Spatio-temporal dynamic diversity of bacterial alkaline phosphatase phoD gene and its environmental drivers in sediments during algal blooms: A case study of shallow Lake Taihu.

Bacterial alkaline phosphatase encoded by the phoD gene is essential for phosphorus (P) cycling in ecosystems. Until now, knowledge of the phoD gene diversity in shallow lake sediments is still lacking. In this study, from early to late stage of cyanobacterial blooms, we investigated the dynamic changes of the abundance of phoD gene (hereafter phoD abundance) and phoD-harboring bacterial community composition (hereafter phoD-harboring BCC) in sediments from different ecological regions of Lake Taihu, the third-largest shallow freshwater lake in China, as well as explored their environmental driving factors. Results showed that phoD abundance in the sediments of Lake Taihu showed spatiotemporal heterogeneity. The highest abundance was found in macrophyte-dominated area (mean 3.25*106copies/g DW), where Haliangium and Aeromicrobium were identified as the major contributors. Due to the negative impact of Microcystis species, phoD abundance decreased significantly (by 40.28% on average) during cyanobacterial blooms in all other regions except the estuary area. The phoD abundance in sediment was positively correlated with total organic carbon (TOC) and total nitrogen (TN). However, the relationship between phoD abundance and alkaline phosphatase activity (APA) varied with time, showing positive correlation (R2 = 0.763, P < 0.01) in the early stage of cyanobacterial blooms, but not (R2 = -0.052, P = 0.838) in the later stage. The predominant phoD-harboring genera in sediments were Kribbella, Streptomyces and Lentzea, all of which belong to Actinobacteria. Non-metric multidimensional scaling (NMDS) analysis revealed that the spatial heterogeneity of phoD-harboring BCC in the sediments of Lake Taihu was significantly higher than the temporal heterogeneity. TP and sand were the principle environmental factors affecting the phoD-harboring BCC in the sediments of the estuary area, while DO, pH, organic phosphorus (Po) and diester phosphorus were the key driving factors for other lake regions. We concluded that the C, N, and P cycles in sediments might work in concert. This study extends the understanding of the phoD gene diversity in shallow lake sediments.

Shen-Qi-Jiang-Tang granule ameliorates diabetic nephropathy via modulating tumor necrosis factor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored. AIM OF THE STUDY: The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments. METHODS AND MATERIALS: The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by H&E, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines. RESULTS: Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment. CONCLUSIONS: SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN.

Ailanthone Inhibits Cell Proliferation in Tongue Squamous Cell Carcinoma via PI3K/AKT Pathway.

Tongue squamous cell carcinoma (TSCC) is the most widespread and invasive subtype of oral cancer with high recurrence rates. Ailanthone (AIL) is an active ingredient in the plant extracts of Ailanthus altissima (Mill.) Swingle. Here, we showed that AIL inhibited the proliferation of human TSCC, the cell viability of Cal-27 and Tca8113 was significantly decreased after AIL treatment for 24 h. Hoechst 33258 staining demonstrated apoptotic characteristics (such as chromatin aggregation) after AIL treatment. The ratio of early- and late-apoptotic cells in AIL-treated Cal-27 and TCA8113 cells increased remarkably when compared with the control group. Bcl-2/Bax ratio and the levels of PARP1, caspase-9, and caspase-3 decreased after AIL treatment, accompanied by significant increase of cleaved PARP1, cleaved caspase-9, and caspase-3 in Cal-27 and TCA8113 cells. Meanwhile, AIL led to Cal-27 cell cycle arrest at G2/M phase. Western blot implied decreased levels of CDK1 and cyclin B1 after AIL treatment. The level of phospho-PI3K p55 subunit and p-Akt were significantly downregulated by AIL in both Cal-27 and TCA8113 cells. These findings implied the potential applications of AIL in the treatment of human TSCC.

Berbamine inhibits RANKL- and M-CSF-mediated osteoclastogenesis and alleviates ovariectomy-induced bone loss.

Osteoporosis is a common public health problem characterized by decreased bone mass, increased bone brittleness and damage to the bone microstructure. Excessive bone resorption by osteoclasts is the main target of the currently used drugs or treatment for osteoporosis. Effective antiresorptive drugs without side effects following long-term administration have become a major focus of anti-osteoporotic drugs. In the present study, we investigated the effect of berbamine, a small molecule natural product from Berberis amurensis Rupr, a traditional Chinese medicine, on RANKL-induced osteoclast differentiation in vitro and ovariectomy-induced bone loss in vivo. The results demonstrated that berbamine at a safe and effective dose inhibited osteoclastogenesis and bone resorption function in vitro by suppressing the nuclear factor-κB signaling pathway. In addition, berbamine protected against osteoporosis by inhibiting osteoclastogenesis and bone resorption function without affecting osteogenesis in the ovariectomy mouse model. These findings revealed that berbamine has a protective role against osteoporosis and may represent a novel promising treatment strategy for osteoporosis.

A research update on the antitumor effects of active components of Chinese medicine ChanSu.

Clinical data show that the incidence and mortality rates of cancer are rising continuously, and cancer has become an ongoing public health challenge worldwide. Excitingly, the extensive clinical application of traditional Chinese medicine may suggest a new direction to combat cancer, and the therapeutic effects of active ingredients from Chinese herbal medicine on cancer are now being widely studied in the medical community. As a traditional anticancer Chinese medicine, ChanSu has been clinically applied since the 1980s and has achieved excellent antitumor efficacy. Meanwhile, the ChanSu active components (e.g., telocinobufagin, bufotalin, bufalin, cinobufotalin, and cinobufagin) exert great antitumor activity in many cancers, such as breast cancer, colorectal cancer, hepatocellular carcinoma and esophageal squamous cell carcinoma. Many pharmaceutical scientists have investigated the anticancer mechanisms of ChanSu or the ChanSu active components and obtained certain research progress. This article reviews the research progress and antitumor mechanisms of ChanSu active components and proposes that multiple active components of ChanSu may be potential anticancer drugs.

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

A Comprehensive Review of C. capsularis and C. olitorius: A Source of Nutrition, Essential Phytoconstituents and Pharmacological Activities.

Plant bioactive compounds have gained global significance in terms of both medicinal and economic ramifications due to being easily accessible and are believed to be effective with fewer side effects. Growing relevant clinical and scientific evidence has become an important criterion for accepting traditional health claims of medicinal plants and also supports the traditional uses of Corchorus as folk medicine. C. capsularis and C. olitorius have broad applications ranging from textile to biocomposite, and young leaves and shoots are used as healthy vegetables and have long been used as traditional remedies for fever, ascites, algesia, liver disorders, piles, and tumors in many cultures. This review systematically summarized and emphasized the nutritional attributes, mostly available bioactive compounds, and biological and potential pharmaceutical properties of C. capsularis and C. olitorius, disclosed to users and non-users. Results suggest that various phytochemicals such as cardiac glycosides, phenols, flavonoids, sterols, lipids, and fatty acids were found or analytically identified in different plant parts (leaf, stem, seed, and root), and many of them are responsible for pharmacological properties and their antitumor, anticancer, antioxidant, antinociceptive, anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticonvulsant, antidiabetic and antiobesity, and cardiovascular properties help to prevent and cure many chronic diseases. In addition to their use in traditional food and medicine, their leaves have also been developed for skin care products, and some other possible uses are described. From this review, it is clear that the isolated compounds of both species have great potential to prevent and treat various diseases and be used as functional foods. In conclusion, this comprehensive review establishes a significant reference base for future research into various medical and functional food applications.

Hernandezine Regulates Proliferation and Autophagy-Induced Apoptosis in Melanoma Cells.

Hernandezine is isolated from an herbal medicine that selectively inhibits multidrug resistance and improves the efficacy of drugs for cancer treatment. To date, no studies on hernandezine in melanoma have been conducted. In this study, hernandezine was found to inhibit proliferation and induce apoptosis in melanoma A375 cells and B16 cells. In hernandezine-treated melanoma cells, G0/G1 cycle arrest occurred accompanied by significantly downregulated levels of phosphorylated JAK2 and STAT3. In addition, the cycle arrest could be enhanced by AG490 (JAK2 inhibitor), suggesting that the JAK2/STAT3 pathway is involved in cell cycle regulation in hernandezine-treated melanoma cells. Hernandezine-treated melanoma cells exhibited autophagy-specific structures, autophagy markers (LC3II/LC3-I), and autophagic flow over time. Moreover, 3-MA (autophagy inhibitor) significantly inhibited apoptosis, indicating that hernandezine promotes apoptosis by inducing autophagy. Combined with differential expression of P-AMPK, P-ACC (downstream targets of adenine monophosphate activated protein kinase, AMPK), and P-p70S6K (downstream targets of mammalian target of rapamycin, mTOR) and significant inhibition of apoptosis by AMPK inhibitor complex C (CC) in hernandezine-treated melanoma cells suggested that hernandezine could induce autophagy via the AMPK-mTOR pathway, thereby inducing apoptosis. This study first analyzed the effect of melanoma cells by hernandezine and provided a theory for hernandezine in the treatment of melanoma.

Luteolin potentiates low-dose oxaliplatin-induced inhibitory effects on cell proliferation in gastric cancer by inducing G2/M cell cycle arrest and apoptosis.

Although the reduction of oxaliplatin doses may alleviate deleterious side effects of gastrointestinal and gynecological cancer treatment, it also limits the anticancer therapeutic effects. As a high-efficient and low-priced herbal medicine ingredient, luteolin is an agent with a broad spectrum of anticancer activities and acts as a potential enhancer of therapeutic effects of chemotherapy agents in cancer treatment. This study focused on the antitumor effects and mechanism of combined treatment with luteolin and oxaliplatin on a mouse forestomach carcinoma (MFC) cell line. The study used CCK-8 assay, flow cytometry, Annexin V-FITC/PI double staining assay, reactive oxygen species testing assay, mitochondrial membrane potential testing assay, and western blot assay. The results showed that luteolin and oxaliplatin exerted synergistic effects on inhibiting MFC cell proliferation by inducing G2/M cell cycle arrest and apoptosis. Inhibiting the tumor necrosis factor receptor-associated protein 1/phosphorylated-extracellular-regulated protein kinases1/2/cell division cycle 25 homolog C/cyclin-dependent kinase-1/cyclin B1 pathway was indispensable to the combined treatment with luteolin and oxaliplatin to induce G2/M cell cycle arrest. In addition, luteolin increased oxidative stress in MFC cells treated with a low dose of oxaliplatin. The combined therapy damaged mitochondrial membrane potential and regulated BCL-2-associated X protein and B-cell lymphoma 2 protein expression, leading to apoptosis. Findings of the present study suggest that luteolin may be a qualified chemotherapy enhancer to potentiate the anticancer effects of low-dose oxaliplatin in MFC cells. This work provides a theoretical foundation for future research on applications of luteolin in clinical chemotherapy.

Suspended particles phoD alkaline phosphatase gene diversity in large shallow eutrophic Lake Taihu.

The bacterial phoD gene encodes alkaline phosphatase plays an important role in the release of bioavailable inorganic phosphorus (P) from organic P in environmental systems. However, phoD gene diversity in suspended particles in shallow freshwater lakes is poorly understood. In this study, we explored the potential relationship between environmental factors and phoD phosphatase gene in suspended particles in different ecosystem types (lake zones) in Lake Taihu, a large shallow eutrophic lake in China. Quantitative PCR and high-throughput sequencing were used to analyze phoD gene abundance and the phoD-harboring bacterial community composition. Our results indicate that the distribution of phoD gene abundance in suspended particles had a high spatiotemporal heterogeneity. The phoD gene abundance in each lake zone decreased significantly from June to September. The dominant phoD-harboring phylum in all samples was Actinobacteria, followed by Proteobacteria, Cyanobacteria and Gemmatimonadetes. The first predominant phoD-harboring genera varied among samples, but most of them belonged to phylum Actinobacteria. Driven by different environmental factors, the phoD-harboring bacterial community structure varied with sampling month and ecosystem type. Nitrate and ammonia nitrogen were the main environmental drivers of phoD-harboring bacterial community in suspended particles in the river mouth zone, while water pH and dissolved oxygen were important factors for the algae-dominated, macrophyte-dominated and central lake zones.

Astragalin Promotes Osteoblastic Differentiation in MC3T3-E1 Cells and Bone Formation in vivo.

Astragalin (AG) is a biologically active flavonoid compound that can be extracted from a number of medicinal plants. However, the effects of AG on osteoblastic differentiation in mouse MC3T3-E1 cells and on bone formation in vivo have not been studied fully. In this study, we found that the activities of alkaline phosphatase (ALP) and mineralized nodules in MC3T3-E1 cells were both significantly increased after treatment with AG (5, 10, and 20 µM). Meanwhile, the mRNA and protein levels of osteoblastic marker genes in MC3T3-E1 cells after AG treatment were markedly increased compared with a control group. In addition, the levels of BMP-2, p-Smad1/5/9, and Runx2 were significantly elevated in AG-treated MC3T3-E1 cells. Moreover, we found that the protein levels of Erk1/2, p-Erk1/2, p38, p-p38, and p-JNK were also significantly increased in AG-treated MC3T3-E1 cells compared to those in the control group. Finally, in vivo experiments demonstrated that AG significantly promoted bone formation in an ovariectomized (OVX)-induced osteoporotic mouse model. This was evidenced by significant increases in the values of osteoblast-related parameters (BFR/BS, MAR, Ob.S/BS, and Ob.N/B.Pm) and bone histomorphometric parameters (BMD, BV/TV, Tb.Th, and Tb.N.) in OVX mice after AG treatment (5, 10, and 20 mg/kg). Collectively, these results demonstrated that AG may promote osteoblastic differentiation in MC3T3-E1 cells via the activation of the BMP and MAPK pathways and promote bone formation in vivo. These novel findings indicated that AG may be a useful bone anabolic agent for the prevention and treatment of osteoporosis.

Flaxseed extract induces apoptosis in human breast cancer MCF-7 cells.

Significant evidence indicated that flaxseed (Linum usitatissimum) possesses various positive health aspects such as reducing the risk of cancer and cardiovascular diseases. The fatty acids are considered to be responsible for these benefits of flaxseed. Herein, the in vitro effects of flaxseed extract on the growth and apoptosis of human breast cancer MCF-7 cells were investigated. The MCF-7 cells treated with flaxseed extract showed a dose-dependent decrease in cell viability. The flaxseed extract induced reactive oxygen species and the flow cytometric analysis demonstrated that flaxseed fatty acids triggered apoptosis of MCF-7 cells, which was also shown by the loss of mitochondrial membrane potential and caspase cascade reaction. Thus, the flaxseed extract regulated the growth of MCF-7 cells and induced apoptosis. Eventually, the flaxseed could be used as a dietary supplement to prevent breast cancer.

Norcantharidin combined with Coix seed oil synergistically induces apoptosis and inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation.

The immune system plays a critical role in exerts effects in the growth and progression of hepatocellular carcinoma (HCC), which needs interacting approaches for effective therapy. In this study, we have found that the Norcantharidin (NCTD) + Coix lacryma-jobi seed oil (CLSO) combination exhibited more potent antitumor effects in an terms of cytotoxicity and apoptotic induction in human HepG2 and HepG2/ADM cells than NCTD or CLSO alone. In vivo, administration of NCTD+CLSO combinations significantly suppressed the formation of tumor in Hepal-1 hepatoma-bearing mice. Furthermore, we found that the in vitro co-cultures of HepG2 or HepG2/ADM cells with PBMCs from healthy donors led to an increase in the number of CD4 + CD25 + T cells. This increase was down-regulated by the combination effectively. Down-regulation of FoxP3 mRNA and protein expression occurred during the combination in the co-cultures. The amount of Tregs of Hepal-1 hepatoma-bearing mice was significantly decreased in the combination treated group. The combination down-regulated the expression of FoxP3, CTLA-4 and Tregs related cytokine (TGF-ß and IL-10) in the serum of tumor bearing mice. Taken together, these results suggest that the most valuable aspect of the NCTD+CLSO combined use improves the anti-tumor activity and regulates tumor infiltrating Tregs.

Molecular Selection, Modification and Development of Therapeutic Oligonucleotide Aptamers.

Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, high production, low cost and high stability, thus are promising inhibitors to rival antibodies for disease therapy. In this review, we will compare the detailed advantages and disadvantages of antibodies and aptamers in therapeutic applications and summarize recent progress in aptamer selection and modification approaches. We will present therapeutic oligonucleotide aptamers in preclinical studies for skeletal diseases and further discuss oligonucleotide aptamers in different stages of clinical evaluation for various disease therapies including macular degeneration, cancer, inflammation and coagulation to highlight the bright commercial future and potential challenges of therapeutic oligonucleotide aptamers.