Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.

https://www.mdpi.com/1660-3397/18/1/8/pdf

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

https://www.mdpi.com/2218-273X/9/8/302/pdf

Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells

As effective non-viral vectors of gene therapy, cationic lipids still have the problem of toxicity, which has become one of the main bottlenecks for their applications. The toxicity of cationic lipids is strongly connected to the headgroup structures. In this article, we studied the cytotoxicity of two cationic lipids with a quaternary ammonium headgroup (CDA14) and a tri-peptide headgroup (CDO14), respectively, and with the same linker bond and hydrophobic domain. The IC50 values of CDA14 and CDO14 against NCI-H460 cells were 109.4 μg mL-1 and 340.5 μg mL-1, respectively. To determine the effects of headgroup structures of cationic lipids on cytotoxicity, apoptosis related pathways were investigated. As the lipids with a quaternary ammonium headgroup could induce more apoptotic cells than the ones with a peptide headgroup, the enzymatic activity of caspase-9 and caspase-3 increased obviously, whereas the mitochondrial membrane potential (MMP) decreased. At the same time, the reactive oxygen species (ROS) levels also increased and the cell cycle was arrested at the S phase. The results showed that the toxicity of the cationic lipid had a close relationship with its headgroup structures, and the cytotoxic mechanism was mainly via the caspase activation dependent signaling pathway and mitochondrial dysfunction. Through this study, we hope to provide the scientific basis for exploiting safer and more efficient cationic lipids for gene delivery.

/pdf/correlation-of-the-cytotoxic-effects-of-cationic-lipids-with-4o5f7bp3z5.pdf

Correlation of the cytotoxic effects of cationic lipids with their headgroups.

// Wei Yu 1,2 , Jian Zhu 1,2 , Yitian Wang 1,2 , Junjie Wang 1,2 , Weijing Fang 1,2 , Kaishun Xia 1,2 , Jianlin Shao 3 , Minzu Wu 4 , Bing Liu 1,2 , Chengzhen Liang 1,2 , Chengyi Ye 1,2 and Huimin Tao 1,2 1 Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China 2 Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, PR China 3 La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA 4 Salk Institute for Biological Studies, La Jolla, CA, USA Correspondence to: Huimin Tao, email: // Keywords : osteosarcoma; photodynamic; target therapy; nanotechnology; immunotherapy Received : November 16, 2016 Accepted : February 07, 2017 Published : March 15, 2017 Abstract Photodynamic therapy, one of the most promising minimally invasive treatments, has received increasing focus in tumor therapy research, which has been widely applied in treating superficial tumors. Three basic factors - photosensitizer, the light source, and oxidative stress - are responsible for tumor cell cytotoxicity. However, due to insufficient luminous flux and peripheral tissue damage, the utilization of photodynamic therapy is facing a huge limitation in deep tumor therapy. Osteosarcoma is the typical deep tumor, which is the most commonly occurring malignancy in children and adolescents. Despite developments in surgery, high risks of the amputation still threatens the health of osteosarcoma patients. In this review, we summarize recent developments in the field of photodynamic therapy and specifically PDT research in OS treatment modalities. In addition, we also provide some novel suggestions, which could potentially be a breakthrough in PDT-induced OS therapies. PDT has the potential to become an effective therapy while the its limitations still present when applied on the treatment of OS or other types of deep tumors. Thus, more researches and studies in the field are required.

/pdf/a-review-and-outlook-in-the-treatment-of-osteosarcoma-and-3uarl8rno7.pdf

A review and outlook in the treatment of osteosarcoma and other deep tumors with photodynamic therapy: from basic to deep.

R-phycoerythrin (R-PE), a marine bioactive protein, is abundant in Porphyra yezoensis with high protein content. In this study, R-PE was purified using a deep eutectic solvents aqueous two-phase system (DES-ATPS), combined with ammonium sulphate precipitation, and characterized by certain techniques. Firstly, choline chloride-urea (ChCl-U) was selected as the suitable DES to form ATPS for R-PE extraction. Then, single-factor experiments were conducted: the purity (A565/A280) of R-PE was 3.825, and the yield was 69.99% (w/w) under optimal conditions (adding 0.040 mg R-PE to ChCl-U (0.35 g)/K2HPO4 (0.8 g/mL, 0.5 mL) and extracting for 20 min). The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results revealed that the purified R-PE contained three main bands. One band was presented after purification in native-PAGE. The UV-vis spectra showed characteristic absorption peaks at 495, 540, and 565 nm. R-PE displayed an emission wavelength at 570 nm when excited at 495 nm. All spectra results illustrated that the structure of R-PE remained unchanged throughout the process, proving the effectiveness of this method. Transmission electron microscope (TEM) showed that aggregation and surrounding phenomena were the driving forces for R-PE extraction. This study could provide a green and simple purification method of R-PE in drug development.

https://www.mdpi.com/1660-3397/18/12/618/pdf

Efficient Purification of R-phycoerythrin from Marine Algae (Porphyra yezoensis) Based on a Deep Eutectic Solvents Aqueous Two-Phase System.

R-Phycoerythrin (R-PE), one of the chemical constituents of red algae, could produce singlet oxygen upon excitation with the appropriate radiation and possibly be used in photodynamic therapy (PDT) for cancer. Documents reported that R-PE could inhibit cell proliferation in HepG2 and A549 cells, which was significative for cancer therapy. This is due to the fact that R-PE could kill cancer cells directly as well as by PDT. However, little is known about the cytotoxicity of R-PE to the SGC-7901 cell. In this study, it has been found that R-PE could inhibit SGC-7901 proliferation and induce cell apoptosis, which was achieved by arresting the SGC-7901 cell at S phase. CyclinA, CDK2 and CDC25A are proteins associated with the S phase, and it was found that R-PE could increase the expression of cyclin A protein and decrease the expression of CDK2 and CDC25A proteins. Thus, it was concluded that R-PE reduced the CDK2 protein activated through decreasing the CDC25A factor, which reduced the formation of Cyclin-CDK complex. The reduction of Cyclin-CDK complex made the SGC-7901 cells arrest at the S phase. Therefore, R-PE induced apoptosis by arresting the SGC-7901 cell at S phase was successful, which was achieved by the expression of the CDC25A protein, which reduced the CDK2 protein actived and the formation of Cyclin-CDK complex.

/pdf/r-phycoerythrin-induces-sgc-7901-apoptosis-by-arresting-cell-5ge26qoxfm.pdf

R-Phycoerythrin Induces SGC-7901 Apoptosis by Arresting Cell Cycle at S Phase.

Kidney disease patients may have concurrent chronic kidney disease-associated mineral bone disorder and hypertension. Cardiovascular disease (CVD) and neuropathy occur due to kidney failure-induced accumulation of uremic toxins in the body. Indoxyl sulfate (IS), a product of indole metabolism in the liver, is produced from tryptophan by the intestinal flora and is ultimately excreted through the kidneys. Hemodialysis helps renal failure patients eliminate many nephrotoxins, except for IS, which leads to a poor prognosis. Although the impacts of IS on cardiac and renal development have been well documented using mouse and rat models, other model organisms, such as zebrafish, have rarely been studied. The zebrafish genome shares at least 70% similarity with the human genome; therefore, zebrafish are ideal model organisms for studying vertebrate development, including renal development. In this study, we aimed to investigate the impact of IS on the development of zebrafish embryos, especially cardiac and renal development. At 24 h postfertilization (hpf), zebrafish were exposed to IS at concentrations ranging from 2.5 to 10 mM. IS reduced survival and the hatching rate, caused cardiac edema, increased mortality, and shortened the body length of zebrafish embryos. In addition, IS decreased heart rates and renal function. IS affected zebrafish development via the ROS and MAPK pathways, which subsequently led to inflammation in the embryos. The results suggest that IS interferes with cardiac and renal development in zebrafish embryos, providing new evidence about the toxicity of IS to aquatic organisms and new insights for the assessment of human health risks. Accordingly, we suggest that zebrafish studies can ideally complement mouse model studies to allow the simultaneous and comprehensive investigation of the physiological impacts of uremic endotheliotoxins, such as IS, on cardiac and renal development.

https://www.mdpi.com/2076-3921/11/2/400/pdf?version=1645584780

Wenhui Guan

Papers

R-Phycoerythrin Induces SGC-7901 Apoptosis by Arresting Cell Cycle at S Phase.

Zebrafish Model-Based Assessment of Indoxyl Sulfate-Induced Oxidative Stress and Its Impact on Renal and Cardiac Development