Sodium Alginate—Natural Microencapsulation Material of Polymeric Microparticles

From the multitude of materials currently available on the market that can be used in the development of microparticles, sodium alginate has become one of the most studied natural anionic polymers that can be included in controlled-release pharmaceutical systems alongside other polymers due to its low cost, low toxicity, biocompatibility, biodegradability and gelatinous die-forming capacity in the presence of Ca²⁺ ions. In this review, we have shown that through coacervation, the particulate systems for the dispensing of drugs consisting of natural polymers are nontoxic, allowing the repeated administration of medicinal substances and the protection of better the medicinal substances from degradation, which can increase the capture capacity of the drug and extend its release from the pharmaceutical form.     

Activated Hepatic Stellate Cells in Hepatocellular Carcinoma: Their Role as a Potential Target for Future Therapies

Hepatocellular carcinoma (HCC) is a global healthcare challenge, which affects more than 815,000 new cases every year. Activated hepatic stellate cells (aHSCs) remain the principal cells that drive HCC onset and growth. aHSCs suppress the anti-tumor immune response through interaction with different immune cells. They also increase the deposition of the extracellular matrix proteins, challenging the reversion of fibrosis and increasing HCC growth and metastasis. Therapy for HCC was reported to activate HSCs, which could explain the low efficacy of current treatments. Conversely, recent studies aimed at the deactivation of HSCs show that they have been able to inhibit HCC growth. In this review article, we discuss the role of aHSCs in HCC pathophysiology and therapy. Finally, we provide suggestions for the experimental implementation of HSCs in HCC therapies.     

The Effects of Genistein at Different Concentrations on MCF-7 Breast Cancer Cells and BJ Dermal Fibroblasts

This study aimed to evaluate the safety and potential use of soy isoflavones in the treatment of skin problems, difficult-to-heal wounds and postoperative scars in women after the oncological treatment of breast cancer. The effects of different concentrations of genistein as a representative of soy isoflavonoids on MCF-7 tumor cells and BJ skin fibroblasts cultured in vitro were assessed. Genistein affects both healthy dermal BJ fibroblasts and cancerous MCF-7 cells. The effect of the tested isoflavonoid is closely related to its concentration. High concentrations of genistein destroy MCF-7 cancer cells, regardless of the exposure time, with a much greater effect on reducing cancer cell numbers at longer times (48 h). Lower concentrations of genistein (10 and 20 μM) increase the abundance of dermal fibroblasts. However, higher concentrations of genistein (50 μM and higher) are detrimental to fibroblasts at longer exposure times (48 h). Our studies indicate that although genistein shows high potential for use in the treatment of skin problems, wounds and surgical scars in women during and after breast cancer treatment, it is not completely safe. Introducing isoflavonoids to treatment requires further research into their mechanisms of action at the molecular level, taking into account genetic and immunological aspects. It is also necessary to conduct research in in vivo models, which will allow for eliminating adverse side effects of therapy.     

Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells

Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications.     

Testing Antimicrobial Properties of Selected Short Amyloids

Amyloids and antimicrobial peptides (AMPs) have many similarities, e.g., both kill microorganisms by destroying their membranes, form aggregates, and modulate the innate immune system. Given these similarities and the fact that the antimicrobial properties of short amyloids have not yet been investigated, we chose a group of potentially antimicrobial short amyloids to verify their impact on bacterial and eukaryotic cells. We used AmpGram, a best-performing AMP classification model, and selected ten amyloids with the highest AMP probability for our experimental research. Our results indicate that four tested amyloids: VQIVCK, VCIVYK, KCWCFT, and GGYLLG, formed aggregates under the conditions routinely used to evaluate peptide antimicrobial properties, but none of the tested amyloids exhibited antimicrobial or cytotoxic properties. Accordingly, they should be included in the negative datasets to train the next-generation AMP prediction models, based on experimentally confirmed AMP and non-AMP sequences. In the article, we also emphasize the importance of reporting non-AMPs, given that only a handful of such sequences have been officially confirmed.     

Polysubstituted Pyrimidines as Potent Inhibitors of Prostaglandin E2 Production: Increasing Aqueous Solubility

Water solubility is one of the key features of potential therapeutic agents. In order to enhance the low water solubility of the parent 5-butyl-4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine, a potent inhibitor of prostaglandin E₂ (PGE₂) production, we synthesized and evaluated a new series of derivatives in which the butyl group at the C5 position of the pyrimidine ring was replaced with a less lipophilic substituent, preferably with a hydrophilic aliphatic moiety. Except for the 5-cyanopyrimidine derivative, all target compounds exhibited increased (2.7–87-fold) water solubility relative to the parent compound. Although nontoxic in mouse peritoneal cells, the prepared compounds were either equipotent or weaker inhibitors of PGE₂ production than the parent compound. The most promising compound from the series was found to be the 5-(2,5,8,11-tetraoxadodecyl)pyrimidine derivative (with three polyethylene glycol units at the C5 position), which exhibited 32-fold higher water solubility and only slightly weaker inhibitory activity (22 % of remaining PGE₂ production) compared with the parent compound (15 % of remaining PGE₂ production).     

Procedurally representing lofted surfaces

The use of tensor-product B-spline surfaces to construct lofted surfaces is discussed. It is shown that several problems must be overcome if tensor-product B-splines are to represent complex lofted surfaces. A method that seems to satisfy all the necessary requirements for parametrically describing such a surface is given. It uses a novel type of surface implemented in a production design system     

Nitric oxide (NO) pathway and locomotor hyperactivity towards dopaminomimetics in rats

The incidence of bladder cancer continues to increase, with an estimated 53,000 new cases diagnosed in the United States in 1996-90% of which are transitional cell carcinomas. The male-to-female ratio is 3:1. A number of etiological factors are associated with the development of bladder cancer, but in industrialized countries, cigarette smoking is the most important. Specific chemicals have also been identified as causing bladder cancer, as have a number of occupational exposures to less well-defined specific agents. Treatment with cytostatic drugs, especially cyclophosphamide, is associated with increased risk of bladder cancer, as is treatment with radiotherapy for uterine cancer. In developing countries, especially in the Middle East and parts of Africa, infections with members of the genus Schistosoma are responsible for a high incidence of bladder cancer-75% of which are squamous cell carcinomas. Arsenic has been indicated as a bladder carcinogen in Argentina, Chile, and Taiwan. The reason for the high incidence of urinary tract cancer in individuals suffering from Balkan nephropathy has yet to be determined. A careful history of patients with bladder cancer is an important and useful process in helping to identify causal factor and, in more than one-half the cases, a known relationship is found. Bladder cancer is a potentially preventable disease, with a significant morbidity and mortality in many parts of the world.     

The fleet size and mix vehicle routing problem

In this paper, we address the problem of routing a fleet of vehicles from a central depot to customers with known demand. Routes originate and terminate at the central depot and obey vehicle capacity restrictions. Typically, researchers assume that all vehicles are identical. In this work, we relax the homogeneous fleet assumption. The objective is to determine optimal fleet size and mix by minimizing a total cost function which includes fixed cost and variable cost components. We describe several efficient heuristic solution procedures as well as techniques for generating a lower bound and an underestimate of the optimal solution. Finally, we present some encouraging computational results and suggestions for further study.