Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs ...from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.
Three lanthanide compounds have been synthesized, namely, {Dy
2
(bpda)
3
(H
2
O)
3
4
·2H
2
O}(Dy-1), {Sm(bpda)
2
·(H
2
O)·H
2
O}
n
(Sm-2) and {Tb
2
(bpda)
3
(H
2
O)
3
4
·2H
2
O} (Tb-3) (H
2
bpda = ...2,2′-bipyridine-6,6′-dicarboxylic acid). Their structures were determined by single crystal X-ray diffraction and characterized by elemental analysis, infrared spectroscopy and thermogravimetric analysis. Dy-1 and Tb-3 are isostructural with a conjugate bimolecular four-nuclear cluster structure constructed with intramolecular hydrogen bonds and they form a 3D supramolecular structure with intermolecular hydrogen bonding. Sm-2 is a one-dimensional chain structure and is further connected by intricate hydrogen bonds into a three-dimensional supramolecular structure. These three compounds exhibit significant characteristic luminescence from the ligand to the central Ln(
iii
) ion, which is found by solid-state photoluminescence measurement. Sm-2 exhibits a long luminescence lifetime and high fluorescence quantum yield. A slow relaxation phenomenon is observed for the dysprosium compound by measuring the alternating-current susceptibility at low temperature and the underlying mechanism was further confirmed by theoretical calculations.
The structures, fluorescence and magnetic properties of series three lanthanide complexes have been investigated. Dysprosium complex exhibit the single-molecule behavior.
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Feature selection is a process aimed at filtering out unrepresentative features from a given dataset, usually allowing the later data mining and analysis steps to produce better results. However, ...different feature selection algorithms use different criteria to select representative features, making it difficult to find the best algorithm for different domain datasets. The limitations of single feature selection methods can be overcome by the application of ensemble methods, combining multiple feature selection results. In the literature, feature selection algorithms are classified as filter, wrapper, or embedded techniques. However, to the best of our knowledge, there has been no study focusing on combining these three types of techniques to produce ensemble feature selection. Therefore, the aim here is to answer the question as to which combination of different types of feature selection algorithms offers the best performance for different types of medical data including categorical, numerical, and mixed data types. The experimental results show that a combination of filter (i.e., principal component analysis) and wrapper (i.e., genetic algorithms) techniques by the union method is a better choice, providing relatively high classification accuracy and a reasonably good feature reduction rate.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The anti-diabetic activity of ginger powder (
) has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies ...presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity. Among the tested compounds, 6-paradol and 6-shogaol showed potent activity in stimulating glucose utilization by 3T3-L1 adipocytes and C2C12 myotubes. The effects were attributed to the increase in 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in 3T3-L1 adipocytes. 6-Paradol, the major metabolite of 6-shogaol, was utilized in an in vivo assay and significantly reduced blood glucose, cholesterol and body weight in high-fat diet-fed mice.
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Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical ...evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC) patients.
We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC). Sixty eligible patients with mCRC were included. Finally, 54 patients were enrolled, of whom 28 were included in the study group and 26 in the control group. The primary endpoint was the disease control rate (DCR), and secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and quality of life (QOL).
The DCRs were 92.8% and 69.2% in the study and control groups, respectively (
= 0.026), in a median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not significantly differ between the two groups.
This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with mCRC. The results indicate that LMF combined with chemotarget agents significantly improved the DCR.
Inflammation is a major cause of skeletal muscle atrophy in various diseases. 2-Hydroxy-4′-methoxychalcone (AN07) is a chalcone-based peroxisome-proliferator-activated receptor gamma (PPARγ) agonist ...with various effects, such as antiatherosclerosis, anti-inflammation, antioxidative stress, and neuroprotection. In this study, we examined the effects of AN07 on protein homeostasis pathway and mitochondrial function in inflammation-associated myotube atrophy induced by lipopolysaccharides (LPS). We found that AN07 significantly attenuated NF-κB activation, inflammatory factors (TNF-α, IL-1β, COX-2, and PGE2), Nox4 expression, and reactive oxygen species levels in LPS-treated C2C12 myotubes. Moreover, AN07 increased SOD2 expression and improved mitochondrial function, including mitochondrial membrane potential and mitochondrial oxygen consumption rate. We also demonstrated that AN07 attenuated LPS-induced reduction of myotube diameter, MyHC expression, and IGF-1/IGF-1R/p-Akt-mediated protein synthesis signaling. Additionally, AN07 downregulated LPS-induced autophagy–lysosomal protein degradation molecules (LC3-II/LC3-I and degraded p62) and ubiquitin–proteasome protein degradation molecules (n-FoxO1a/MuRF1/atrogin-1). However, the regulatory effects of AN07 on protein synthesis and degradation signaling were inhibited by the IGF-1R inhibitor AG1024 and the PI3K inhibitor wortmannin. In addition, the PPARγ antagonist GW9662 attenuated the effects of AN07 against LPS-induced inflammation, oxidation, and protein catabolism. In conclusion, our findings suggest that AN07 possesses protective effects on inflammation-induced myotube atrophy and mitochondrial dysfunction.
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Most chemotherapeutic drugs for killing cancer cells are highly cytotoxic in normal cells, which limits their clinical applications. Therefore, a continuing challenge is identifying a drug that is ...hypersensitive to cancer cells but has minimal deleterious effects on healthy cells. The aims of this study were to evaluate the potential of 4β-hydroxywithanolide (4βHWE) for selectively killing cancer cells and to elucidate its related mechanisms.
Changes in survival, oxidative stress, DNA damage, and apoptosis signaling were compared between 4βHWE-treated oral cancer (Ca9-22) and normal fibroblast (HGF-1) cells. At 24 h and 48 h, the numbers of Ca9-22 cells were substantially decreased, but the numbers of HGF-1 cells were only slightly decreased. Additionally, the IC50 values for 4βHWE in the Ca9-22 cells were 3.6 and 1.9 µg/ml at 24 and 48 h, respectively. Time-dependent abnormal increases in ROS and dose-responsive mitochondrial depolarization can be exploited by using 4βHWE in chemotherapies for selectively killing cancer cells. Dose-dependent DNA damage measured by comet-nuclear extract assay and flow cytometry-based γ-H2AX/propidium iodide (PI) analysis showed relatively severer damage in the Ca9-22 cells. At both low and high concentrations, 4βHWE preferably perturbed the cell cycle in Ca9-22 cells by increasing the subG1 population and arrest of G1 or G2/M. Selective induction of apoptosis in Ca9-22 cells was further confirmed by Annexin V/PI assay, by preferential expression of phosphorylated ataxia-telangiectasia- and Rad3-related protein (p-ATR), and by cleavage of caspase 9, caspase 3, and poly ADP-ribose polymerase (PARP).
Together, the findings of this study, particularly the improved understanding of the selective killing mechanisms of 4βHWE, can be used to improve efficiency in killing oral cancer cells during chemoprevention and therapy.
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In an attempt to explore the bioactive metabolites of the soft coral
, three new cembranolides, cinerenolides A-C (
-
), and 16 known compounds were isolated and identified from the EtOAc extract. ...The structures of the new cembranolides were elucidated on the basis of spectroscopic analysis, and the NOE analysis of cinerenolide A (
) was performed with the assistance of the calculated lowest-energy molecular model. The relative configuration of cinerenolide C (
) was determined by the quantum chemical NMR calculation, followed by applying DP4+ analysis. In addition, the cytotoxic assays disclosed that some compounds exhibited moderate to potent activities in the proliferation of P388, DLD-1, HuCCT-1, and CCD966SK cell lines.
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Exosomes are cell-derived membranous structures primarily involved in the delivery of the payload to the recipient cells, and they play central roles in carcinogenesis and metastasis. Radiotherapy is ...a common cancer treatment that occasionally generates exosomal miRNA-associated modulation to regulate the therapeutic anticancer function and side effects. Combining radiotherapy and natural products may modulate the radioprotective and radiosensitizing responses of non-cancer and cancer cells, but there is a knowledge gap regarding the connection of this combined treatment with exosomal miRNAs and their downstream targets for radiation and exosome biogenesis. This review focuses on radioprotective natural products in terms of their impacts on exosomal miRNAs to target radiation-modulating and exosome biogenesis (secretion and assembly) genes. Several natural products have individually demonstrated radioprotective and miRNA-modulating effects. However, the impact of natural-product-modulated miRNAs on radiation response and exosome biogenesis remains unclear. In this review, by searching through PubMed/Google Scholar, available reports on potential functions that show radioprotection for non-cancer tissues and radiosensitization for cancer among these natural-product-modulated miRNAs were assessed. Next, by accessing the miRNA database (miRDB), the predicted targets of the radiation- and exosome biogenesis-modulating genes from the Gene Ontology database (MGI) were retrieved bioinformatically based on these miRNAs. Moreover, the target-centric analysis showed that several natural products share the same miRNAs and targets to regulate radiation response and exosome biogenesis. As a result, the miRNA-radiomodulation (radioprotection and radiosensitization)-exosome biogenesis axis in regard to natural-product-mediated radiotherapeutic effects is well organized. This review focuses on natural products and their regulating effects on miRNAs to assess the potential impacts of radiomodulation and exosome biogenesis for both the radiosensitization of cancer cells and the radioprotection of non-cancer cells.
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Hepatitis C virus (HCV) is an important human pathogen leading to hepatocellular carcinoma. Using an in vitro cell-based HCV replicon and JFH-1 infection system, we demonstrated that an aqueous ...extract of the seaweed Gracilaria tenuistipitata (AEGT) concentration-dependently inhibited HCV replication at nontoxic concentrations. AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment. We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels. Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects. Furthermore, we highlighted the inhibitory effect of AEGT in HCV-induced pro-inflammatory gene expression such as the expression of tumour necrosis factor-α, interleukin-1β, inducible nitrite oxide synthase and COX-2 in a concentration-dependent manner to evaluate the potential therapeutic supplement in the management of patients with chronic HCV infections.
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