Algae in Biomedicine.

Algae, which live in marine or freshwater, are photosynthetic organisms. They vary greatly in size, morphology, and degree of complexity of their body structures. Algae are generally divided into two main groups, microalgae, which are small in size, and macroalgae, which are larger in size. These aquatic organisms have rich and valuable compounds including sterols, polysaccharides, pigments, fatty acids, proteins, enzymes, minerals, and vitamins that could be used in different application fields due to their bioactive functions. In recent years, algae and their components have attracted interest in biomedicine and health applications as their bioactive components could show antioxidant, anticancer, anti-inflammatory, antiviral, antiangiogenic, antidiabetic, antiobesity, immunostimulatory, vaccine adjuvant, and hypolipidemic activities. In this chapter, these activities and bioactive components underlying these properties are reviewed.

Aligned with sustainable development goals: microwave extraction of astaxanthin from wet algae and selective cytotoxic effect of the extract on lung cancer cells.

Astaxanthin is one of the most attractive carotenoid in the cosmetic, food, pharmaceutical, and aquaculture industries due to its strong bioactive properties. Among the various sources, several algae species are considered as rich sources of astaxanthin. Downstream processing of algae involves the majority of the total processing costs. Thus, elimination of high energy involved steps is imperative to achieve cost-effective scale in industry. This study aimed to determine operation conditions for astaxanthin extraction from wet Haematococcus pluvialis using microwave-assisted extraction. The isolated astaxanthin extract was evaluated for cytotoxicity on human lung cancer cells. The microwave-assisted extraction process at 75 °C under the power of 700 Watt for 7 min gave the highest astaxanthin yield (12.24 ± 0.54 mg astaxanthin/g wet cell weight). Based on MTT cell viability and Hoechst 33342 nuclear staining assays on A549 lung cancer cells, astaxanthin inhibited cell growth in dose- and time-dependent manners, where IC50 value was determined as 111.8 ± 14.8 µg/mL and apoptotic bodies were observed along with positive control group at 72 hr. These results showed that the treatment with astaxanthin extracted from wet H. pluvialis by microwave-assisted extraction exhibited anti-cancer activity on lung cancer cells indicating a newly potential to be utilized in industry.

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes.

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.

Experimental design methods for bioengineering applications.

Experimental design is a form of process analysis in which certain factors are selected to obtain the desired responses of interest. It may also be used for the determination of the effects of various independent factors on a dependent factor. The bioengineering discipline includes many different areas of scientific interest, and each study area is affected and governed by many different factors. Briefly analyzing the important factors and selecting an experimental design for optimization are very effective tools for the design of any bioprocess under question. This review summarizes experimental design methods that can be used to investigate various factors relating to bioengineering processes. The experimental methods generally used in bioengineering are as follows: full factorial design, fractional factorial design, Plackett-Burman design, Taguchi design, Box-Behnken design and central composite design. These design methods are briefly introduced, and then the application of these design methods to study different bioengineering processes is analyzed.

The effect of folic acid supplementation and folate deficiency on embryo implantation.

Implantation is a critical stage of pregnancy, which occurs in a short period of interaction between the receptive endometrium and the embryo. Folic acid (FA) is a synthetic derivative of folate and is recommended as a pre-conceptional supplement. However, the impact of different doses of FA supplementation and folate deficiency during the early stages of pregnancy requires further investigation. The aim of this study was to investigate the possible effects of FA supplementation and folate deficiency on expression of Estrogen Receptor Alpha (ER-α), Vascular Endothelial Growth Factor-A (VEGFA), and Integrin alpha V and beta3 (Integrin αVß3). A total of 32, 6-8-week old Wistar albino rats were divided into four groups of control, folate-deficiency, low-dose, and high-dose FA supplement groups. After five weeks of FA supplementation and folate deficiency model formation, mated rats were sacrificed on the 5th gestational day (GD), and implantation sites were collected. The expression of ER- α, VEGFA, and Integrin αVß3 in the implantation sites were examined with immunohistochemistry and real-time PCR. The results revealed that the mRNA levels of ESR1, VEGFA, and Integrin αV and ß3 were significantly increased in the high-dose FA group and significantly decreased in the folate deficiency group compared to the control group (p < 0.05). Based on these results, it can be concluded that FA supplementation before pregnancy has positive effects on the maintenance of pregnancy, and folate deficiency may lead to implantation disorders.

Volumetric Mass Transfer Coefficient Measurement in a Stirred Tank Reactor.

A bioreactor is a controlled vessel which provides biological conversions into bioactive components using cells or enzymes. In the aerobic processes, it is important to know oxygen requirements of the cells which may vary during fermentation as a result of microbial activity, aging, substrate depletion and product formation, etc. Here we describe the measurement of volumetric mass transfer coefficient (k L a) in a stirred tank reactor using dynamic method based on unsteady state which is also one of the significant parameter especially in scaling-up. The equipment in the measurement according to dynamic method has low cost compared to steady-state methodology. This method is reliable in the determination of k L a when the gas residence time and probe measuring the oxygen concentration of response time are in specific requirements.

Key Challenges of Microbial Degradation of Keratinous Wastes.

Feather is the main waste of poultry industries and constitutes of 90% keratin. Wastes composed of keratin are insoluble and recalcitrant to degradation using conventional decomposing methods. Microbial degradation for keratinous wastes is a promising approach for being eco-friendly and economically. However, due to insolubility of keratinous waste, it has several challenges in upstream and downstream processes such as culture medium optimization, designing of bioreactor, bioreaction/flow type, bioreactor configurations considering mass and heat transfer limitations, rheology derived problems, monitoring of microbial activity, choosing of the right scale-up parameter and purification. In this study, the challenges for keratin degradation processes were discussed with the aim of opening new opportunities for keratinous waste treatments in industrial level.

Effect of Agitation and Aeration on Keratinase Production in Bioreactors Using Bioprocess Engineering Aspects.

Streptomyces sp. 2M21 was evaluated for keratinase production in bioreactors using chicken feathers. Firstly, optimization of bioengineering parameters (agitation and aeration rates) using Response Surface Methodology was carried out in 2 L bioreactors. Optimized conditions identified by the modified quadratic model were verified as 150 rpm and 1 vvm experimentally corresponding to 351 U/ml of keratinase activity. Moreover, scaling up sequentially to 20 L bioreactors was implemented using constant impeller tip speed and constant mass transfer coefficient as key scale-up parameters. The keratinase activity in 5, 10 and 20 L bioreactors showed similar results with the one of shake flasks (412 U/ml) and 2 L bioreactors (351 U/ml)with respect to the keratinase activity values of 336, 385 and 344 U/ml, respectively. The results suggest keratinase production by evaluating chicken feathers in commercial level. Furthermore, this study has potential to contribute industrial scale production of keratinase by Streptomyces sp. 2M21 using the proposed bioreactor conditions.

Scaling-up of Haematococcus pluvialis production in stirred tank photobioreactor.

The objective of this study was to evaluate three most common scale-up criteria for Haematococcus pluvialis production from cultivation bottles to 2 and 10 L of stirred tank PBRs. Constant volumetric power input (P/V) was found to be the most suitable criterion for H. pluvialis production. Total carotenoid amount per biomass concentration in 2 L and 10 L stirred tank PBRs were determined to be 4.57 mg/g and 4.77 mg/g, respectively. Antioxidant activity of total carotenoids extracted from H. pluvialis was also higher at constant P/V criterion where 46.91% inhibition rate with a total phenolic content of 11.76 mg gallic acid/L was achieved. Obtained results could be used to expand the bioproduction of H. pluvialis and its extracts in commercial scale.

Computational fluid dynamics simulation in scaling-up of airlift photobioreactor for astaxanthin production.

The unicellular green microalga Haematococcus pluvialis accumulates large amounts of the red ketocarotenoid astaxanthin. Aiming to cultivate these microalgae with high astaxanthin efficiency, cultivations were scaled-up from 1000 mL bottle to 2 L and 8 L airlift photobioreactor using volumetric power consumption rate (W/m3) as scale up strategy. After cultivations, computational fluid dynamics (CFD) simulation was used to investigate the flow patterns, mixing efficiency and gas holdup profile within the 2 L photobioreactor. At the end, astaxanthin content was enhanced with increasing the cultivation volume and highest astaxanthin amount of 49.39 ± 1.64 mg/g cell was obtained in 8 L photobioreactor. Hydrodynamic characteristics of photobioreactor was simulated and gas holdup showed difference between the riser and the downcomer regions. Velocity profiles of air and medium had higher values inside the draft tube than obtained in downcomer region. However liquid circulation was achieved from draft tube to the downcomer, mixing was not provided effectively considering the turbulence kinetic energy. For the further research, some developments about column configuration, sparger diameter may be necessary to enhance the mixing characteristics.