Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating “click reaction” with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC₅₀ < 0.01 mg mL⁻¹) was more efficient than that of derivatives with triazole and Vitamin C. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains. Full article

Sepia ink polysaccharide (SIP) isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami), cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents. Full article

Acquired drug resistance constitutes an enormous hurdle in cancer treatment, and the search for effective compounds against resistant cancer is still advancing. Marine organisms are a promising natural resource for the discovery and development of anticancer agents. In this study, we examined whether gliotoxin (GTX), a secondary metabolite isolated from marine-derived Aspergillus fumigatus, inhibits the growth of adriamycin (ADR)-resistant non-small-cell lung cancer (NSCLC) cell lines A549/ADR. We investigated the effects of GTX on A549/ADR cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the induction of apoptosis in A549/ADR cells treated with GTX via fluorescence-activated cell sorting analysis, Hoechst staining, annexin V/propidium iodide staining, tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and western blotting. We found that GTX induced apoptosis in A549/ADR cells through the mitochondria-dependent pathway by disrupting mitochondrial membrane potential and activating p53, thereby increasing the expression levels of p21, p53 upregulated modulator of apoptosis (PUMA), Bax, cleaved poly (ADP-ribose) polymerase (PARP), and cleaved caspase-9. More importantly, we discovered that GTX works in conjunction with ADR to exert combinational effects on A549/ADR cells. In conclusion, our results suggest that GTX may have promising effects on ADR-resistant NSCLC cells by inducing mitochondria-dependent apoptosis and through the combined effects of sequential treatment with ADR. Full article

The 7-Acetylsinumaximol B (7-AB), a bioactive cembranoid, was originally discovered from aquaculture soft coral Sinularia sandensis. The current study investigated the anti-proliferative property of 7-AB towards the NCI-N87 human gastric cancer cell line. An MTT cell proliferative assay was applied to evaluate cell survival, and immunofluorescence staining and western blotting were employed to analyze the effects of 7-AB on autophagy and apoptosis. Our results showed that 7-AB exerted a concentration-dependent anti-proliferative effect on NCI-N87 cells, and fluorescence staining indicated that the effect was due to the apoptosis induced by 7-AB. In addition, the 7-AB-induced anti-proliferation towards NCI-N87 cells was associated with the release of cytochrome c from mitochondria, activation of pro-apoptotic proteins (such as caspase-3/-9, Bax and Bad), and inhibition of anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1). The 7-AB treatment also triggered endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/ATF4/CHOP apoptotic pathway. Furthermore, 7-AB initiated autophagy in NCI-N87 cells and induced the expression of autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12, LC3-I, and LC3-II. Taken together, our findings suggested that 7-AB has the potential to be further developed as a useful anti-cancer or adjuvant agent for the treatment of human gastric cancer. Full article

A new prenyleudesmane type diterpene, sinupol (8), and a new capnosane type diterpenoid, sinulacetate (9), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes (4–7 and 10). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds (8 and 9) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity. Full article

The challenge to develop grafts for tissue regeneration lies in the need to obtain a scaffold that will promote cell growth in order to form new tissue at a trauma-damaged site. Scaffolds also need to provide compatible mechanical properties that will support the new tissue and facilitate the desired physiological activity. Here, we used natural materials to develop a bio-composite made of unique collagen embedded in an alginate hydrogel material. The collagen fibers used to create the building blocks exhibited a unique hyper-elastic behavior similar to that of natural human tissue. The prominent mechanical properties, along with the support of cell adhesion affects cell shape and supports their proliferation, consequently facilitating the formation of a new tissue-like structure. The current study elaborates on these unique collagen fibers, focusing on their structure and biocompatibility, in an in vitro model. The findings suggest it as a highly appropriate material for biomedical applications. The promising in vitro results indicate that the distinctive collagen fibers could serve as a scaffold that can be adapted for tissue regeneration, in support of healing processes, along with maintaining tissue mechanical properties for the new regenerate tissue formation. Full article

Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are ubiquitously found in different tissues but, are abundant in shark liver oil, breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are commercially available, while many others with saturated or mono-unsaturated alkyl chains of variable length are not available. These compounds are, however, necessary as standards for analytical methods. Here, we investigated different reported procedures and we adapted some of them to prepare a series of 1-O-alkyl-glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0, 17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these standards were fully characterized by NMR and GC-MS. Finally, we used these standards to identify the AEL subtypes in shark and chimera liver oils. The distribution of the identified AEL were: 14:0 (20–24%), 16:0 (42–54%) and 18:1 (6–16%) and, to a lesser extent, (0.2–2%) for each of the following: 16:1, 17:0, 18:0, and 20:0. These standards open the possibilities to identify AEL subtypes in tumours and compare their composition to those of non-tumour tissues. Full article

In the experiment, crude proteins from spotless smoothhound (Mustelus griseus), cartilages were isolated by HCl-Guanidine buffer, and its hydrolysate was prepared using trypsin at pH 8.0, 40 °C with a total enzyme dose of 2.5%. Subsequently, three antioxidant peptides were purified from the hydrolysate using membrane ultrafiltration, anion-exchange chromatography, gel filtration chromatography, and reverse phase high-performance liquid chromatography. The amino acid sequences of isolated peptides were identified as Gly-Ala-Glu-Arg-Pro (MCPE-A); Gly-Glu-Arg-Glu-Ala-Asn-Val-Met (MCPE-B); and Ala-Glu-Val-Gly (MCPE-C) with molecular weights of 528.57, 905.00, and 374.40 Da, respectively, using protein amino acid sequence analyzer and mass spectrum. MCPE-A, MCPE-B and MCPE-C exhibited good scavenging activities on 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) (EC₅₀ 3.73, 1.87, and 2.30 mg/mL, respectively), hydroxyl radicals (HO•) (EC₅₀ 0.25, 0.34, and 0.06 mg/mL, respectively), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radicals (ABTS⁺•) (EC₅₀ 0.10, 0.05, and 0.07 mg/mL, respectively) and superoxide anion radicals ( ${\mathrm{O}}_2^{-}$ •) (EC₅₀ 0.09, 0.33, and 0.18 mg/mL, respectively). MCPE-B showed similar inhibiting ability on lipid peroxidation with butylated hydroxytoluene (BHT) in a linoleic acid model system. Furthermore, MCPE-A, MCPE-B, and MCPE-C could protect H₂O₂-induced HepG2 cells from oxidative stress by decreasing the content of malonaldehyde (MDA) and increasing the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx). Glu, Gly, Met, and Pro in their sequences and low molecular weight could be attributed to the antioxidant activities of three isolated peptides. These results suggested that GAERP (MCPE-A), GEREANVM (MCPE-B), and AEVG (MCPE-C) from cartilage protein hydrolysate of spotless smoothhound might serve as potential antioxidants and be used in the pharmaceutical and health food industries. Full article

Soft corals are known to be prolific producers of a wide spectrum of biologically active cembranoids. One new cembranoid, sinularolide F (2), along with three known compounds, cembranolide (1), (E,E,E)-6,10,14-trimethyl-3-methylene-cis-3α,4,5,8,9,12,13,15α-octahydrocyclo tetradeca[β]furan-2(3H)-one (3), and denticulatolide (4), were isolated from the Bornean soft coral Sinularia sp. Compounds 2 and 4 showed potential anti-inflammatory activities against lipopolysaccharide-stimulated RAW 264.7 with IC₅₀ values less than 6.25 µg/mL and anticancer activity against HL60 cell lines. The compounds’ mechanisms of action were investigated via the Western blot evaluation of their protein markers. These activities could be attributed to the presence of tertiary methyl at C-8 and the compounds’ 3D configurations. Full article