Cell Culture Model Evolution and Its Impact on Improving Therapy Efficiency in Lung Cancer.

Optimizing cell culture conditions is essential to ensure experimental reproducibility. To improve the accuracy of preclinical predictions about the response of tumor cells to different classes of drugs, researchers have used 2D or 3D cell cultures in vitro to mimic the cellular processes occurring in vivo. While 2D cell culture provides valuable information on how therapeutic agents act on tumor cells, it cannot quantify how the tumor microenvironment influences the response to therapy. This review presents the necessary strategies for transitioning from 2D to 3D cell cultures, which have facilitated the rapid evolution of bioengineering techniques, leading to the development of microfluidic technology, including organ-on-chip and tumor-on-chip devices. Additionally, the study aims to highlight the impact of the advent of 3D bioprinting and microfluidic technology and their implications for improving cancer treatment and approaching personalized therapy, especially for lung cancer. Furthermore, implementing microfluidic technology in cancer studies can generate a series of challenges and future perspectives that lead to the discovery of new predictive markers or targets for antitumor treatment.

Ganoderma lucidum-Mediated Green Synthesis of Silver Nanoparticles with Antimicrobial Activity.

"Green chemistry" is a simple and easily reproductible method that provides nanoparticles characterized by better stability and good dispersion in an aqueous solution. Nanoparticles can be synthesized by algae, bacteria, fungi, and plant extracts. Ganoderma lucidum is a commonly used medicinal mushroom with distinctive biological properties, such as antibacterial, antifungal, antioxidant, anti-inflammatory, anticancer, etc. In this study, aqueous mycelial extracts of Ganoderma lucidum were used to reduce AgNO3 to form silver nanoparticles (AgNPs). The biosynthesized nanoparticles were characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) analysis. The maximum UV absorption was obtained at 420 nm, which represents the specific surface plasmon resonance band for biosynthesized silver nanoparticles. SEM images showed particles as predominantly spherical, while FTIR spectroscopic studies illustrated the presence of functional groups that can support the reducing of ion Ag+ to Ag(0). XRD peaks ratified the presence of AgNPs. The antimicrobial effectiveness of synthesized nanoparticles was tested against Gram-positive and Gram-negative bacterial and yeasts strains. The silver nanoparticles were effective against pathogens, inhibiting their proliferation, and thus reducing the risk to the environment and to public health.

Potential Antitumor Effect of Functional Yogurts Formulated with Prebiotics from Cereals and a Consortium of Probiotic Bacteria.

Various types of functional yogurts were obtained from normalized milk (with normalized lipid content) and a standardized probiotic consortium of probiotic bacteria named ABY3. All the types of yogurts obtained contained prebiotics from black or red rice; malt of barley, rye, wheat; or wheat bran. The physico-chemical analyses of all the functionalized products obtained showed that all of them met the quality standard for yogurt products. However, the sensorial analyses showed that the products obtained from black and red rice were of very good quality. The biological analyses indicated that all the types of products contained live probiotic bacteria, but wheat bran and red rice could increase their numbers. Tests performed on tumor cell line Caco-2 with corresponding postbiotics revealed cytotoxicity greater than 30% after 48 h of exposure in the case of yogurts obtained from milk with 0.8% lipid content and red rice or blond malt of barley. In the case of yogurts derived from milk with 2.5% lipid content, only the variants that contained blond malt of rye or wheat became cytotoxic against the Caco-2 cell line.

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene.

The paper presents the results of the studies performed to establish the effect of the mixtures between limonene and clotrimazole against microbial pathogens involved in dermatological diseases, such as Candida albicans, Staphyloccocus aureus, and Escherichia coli. Preliminary data obtained from the studies performed in microplates revealed a possible synergism between the mixture of clotrimazole and limonene for Staphylococcus aureus. Studies performed "in silico" with programs such as CLC Drug Discovery Workbench and MOLEGRO Virtual Docker, gave favorable scores for docking each compound on a specific binding site for each microorganism. The tests performed for validation, with the clotrimazole (0.1%) and different sources of limonene (1.9% citrus essential oils), showed a synergistic effect on Staphylococcus aureus in the case of the mixtures between clotrimazole and the essential oils of Citrus reticulata or Citrus paradisi. The studies performed on Staphylococcus aureus MRSA showed a synergistic effect between clotrimazole and the essential oils obtained from Citrus bergamia, Citrus aurantium, or Citrus paradisi. In the case of Pseudomonas aeruginosa, essential oils and clotrimazole used alone did not exhibit antimicrobial activities, but the mixtures between clotrimazole and the essential oils of Citrus bergamia or Citrus sinensis exhibited a synergistic antimicrobial effect.

Highlighting Bacteria with Calcifying Abilities Suitable to Improve Mortar Properties.

Biomineralization, the use of microorganisms to produce calcium carbonate, became a green solution for application in construction materials to improve their strength and durability. The calcifying abilities of several bacteria were investigated by culturing on a medium with urea and calcium ions. The characterization of the precipitates from bacterial cultures was performed using X-ray diffraction, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The formation of carbonate crystals was demonstrated by optical and scanning electron microscopy. Water absorption and compressive strength measurements were applied to mortars embedded with sporal suspension. The efficiency of the supplementation of mortar mixtures with bacterial cells was evaluated by properties, namely the compressive strength and the water absorption, which are in a relationship of direct dependence, the increase in compressive strength implying the decrease in water absorption. The results showed that Bacillus subtilis was the best-performing bacterium, its introduction into the mortar producing an increase in compressive strength by 11.81% and 9.50%, and a decrease in water absorption by 11.79% and 10.94%, after 28 and 56 days of curing, respectively, as compared to standards. The exploitation of B. subtilis as a calcifying agent can be an interesting prospect in construction materials.

Obtaining and Characterizing Composite Biomaterials of Animal Resources with Potential Applications in Regenerative Medicine.

Raw materials, such as collagen and chitosan, obtained from by-products from the food industry (beef hides and crustacean exoskeletons), can be used to obtain collagen-chitosan composite biomaterials, with potential applications in regenerative medicine. Functionalization of these composite biomaterials is a possibility, thus, resulting in a molecule with potential applications in regenerative medicine, namely clotrimazole (a molecule with antibacterial, antifungal, and antitumor activity), at a mass ratio (collagen-chitosan-clotrimazole) of 1:1:0.1. This functionalized composite biomaterial has great potential for application in regenerative medicine, due to the following properties: (1) it is porous, and the pores formed are interconnected, due to the use of a mass ratio between collagen and chitosan of 1:1; (2) the size of the formed pores is between 500-50 µm; (3) between collagen and chitosan, hydrogen bonds are formed, which ensure the unity of composite biomaterial; (4) the functionalized bio-composite exhibits in vitro antimicrobial activity for Candida albicans, Staphylococcus aureus, and Staphylococcus aureus MRSA; for the latter microorganism, the antimicrobial activity is equivalent to that of the antibiotic Minocycline; (5) the proliferation tests performed on a standardized line of normal human cells with simple or composite materials obtained by lyophilization do not show cytotoxicity in the concentration range studied (10-500) µg/mL.

Studies Regarding the Pharmaceutical Potential of Derivative Products from Plantain.

In this study, three types of extracts isolated from leaves of Plantain (Plantago lanceolata) were tested for their chemical content and biological activities. The three bioproducts are combinations of polysaccharides and polyphenols (flavonoids and iridoidic compounds), and they were tested for antioxidant, antifungal, antitumor, and prebiotic activity (particularly for polysaccharides fraction). Briefly, the iridoid-enriched fraction has revealed a pro-oxidant activity, while the flavonoid-enriched fraction had a high antioxidant potency; the polysaccharide fraction also indicated a pro-oxidant activity, explained by the co-presence of iridoid glycosides. All three bioproducts demonstrated moderate antifungal effects against Aspergillus sp., Penicillium sp., and dermatophytes, too. Studies in vitro proved inhibitory activity of the three fractions on the leukemic tumor cell line THP-1, the main mechanism being apoptosis stimulation, while the polysaccharide fraction indicated a clear prebiotic activity, in the concentration range between 1 and 1000 µg/mL, evaluated as higher than that of the reference products used, inulin and dextrose, respectively.

Medlar-A Comprehensive and Integrative Review.

Among fruit plants belonging to the Rosaceae family, medlar (Mespilus) can be classified as neglected or underutilized. It is a genus of two species of flowering plants: Mespilus germanica (common medlar) and Mespilus canescens. Appreciated for its specific taste and flavor, medlar also possesses biological properties (antioxidant and antimicrobial). Despite the special properties of medlar, there are few research papers on this subject. This review paper includes data not only on medlar fruits but also its leaves, bark, and bud flowers. The main identified components are presented, as well as several biological properties, morphological properties, ethnopharmacological uses, and molecular biology analyses emerging from the scientific papers published in this area.

Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines.

In head and neck cancers, the effectiveness of cisplatin (CisPt) treatment is limited by its toxicity, especially when higher doses are necessary, and the possible occurrence of cisplatin resistance. This study evaluated the effects of resveratrol (RSV) on the expression of different genes involved in the response of human tumor cells (FaDu, PE/CA-PJ49) to cisplatin therapy. Our results revealed that RSV induced apoptosis amplification in both FaDu and PE/CA-PJ49 cells and modulated the expression of specific genes differently than in normal HaCaT cells. In FaDu cells, combined CisPt + RSV treatment induced an increase in apoptosis, which was associated with an increase in c-MYC and TP53 and a decrease in BCL-2 expression. While CisPt + RSV treatment induced apoptosis in PE/CA-PJ49 cells by inhibition of BCL-2 associated with high levels of MDM-2 and subsequently led to inhibition of TP53 gene expression. Decreased c-MYC expression in PE/CA-PJ49 treated with CisPt + RSV was accompanied by cell cycle blockage in G0/G1 phase. In conclusion, RSV influences tumor cell response to CisPt by inducing apoptosis and modulating gene expression. In addition, in normal HaCaT cells, RSV was able to reduce the harmful effects of CisPt.

Fungal Based Biopolymer Composites for Construction Materials.

Environmental contamination, extensive exploitation of fuel sources and accessibility of natural renewable resources represent the premises for the development of composite biomaterials. These materials have controlled properties, being obtained through processes operated in mild conditions with low costs, and contributing to the valorization of byproducts from agriculture and industry fields. A novel board composite including lignocelullosic substrate as wheat straws, fungal mycelium and polypropylene embedded with bacterial spores was developed and investigated in the present study. The bacterial spores embedded in polymer were found to be viable even after heat exposure, helping to increase the compatibility of polymer with hydrophilic microorganisms. Fungal based biopolymer composite was obtained after cultivation of Ganoderma lucidum macromycetes on a mixture including wheat straws and polypropylene embedded with spores from Bacillus amyloliquefaciens. Scanning electron microscopy (SEM) and light microscopy images showed the fungal mycelium covering the substrates with a dense network of filaments. The resulted biomaterial is safe, inert, renewable, natural, biodegradable and it can be molded in the desired shape. The fungal biocomposite presented similar compressive strength and improved thermal insulation capacity compared to polystyrene with high potential to be used as thermal insulation material for applications in construction sector.

Ciprofloxacin-Collagen-Based Materials with Potential Oral Surgical Applications.

We report in this paper the synthesis and characterization of a new collagen-based material. This material was obtained in a spongy form and was functionalized with an antibiotic, ciprofloxacin. The targeted applications of these kind of materials concern the post-operative prophylaxis. The in vitro tests (antimicrobial, cytotoxic, drug release) showed that sponges with a concentration of 0.75 g of ciprofloxacin per gram of collagen could be beneficial for the desired applications.

The Effect of Resveratrol or Curcumin on Head and Neck Cancer Cells Sensitivity to the Cytotoxic Effects of Cisplatin.

Natural compounds can modulate all three major phases of carcinogenesis. The role of the natural compounds such as resveratrol (RSV) and curcumin (CRM) in modulation of anticancer potential of platinum-based drugs (CisPt) is still a topic of considerable debate. In order to enhance head and neck cancer (HNSCC) cells' sensitivity to the cytotoxic effects of CisPt combined treatments with RSV or CRM were used. The study aim was to evaluate how the RSV or CRM associated to CisPt treatment modulated some cellular processes such as proliferation, P21 gene expression, apoptotic process, and cell cycle development in HNSCC tumor cell line (PE/CA-PJ49) compared to a normal cell line (HUVEC). The results showed that RSV or CRM treatment affected the viability of tumor cells more than normal cells. These natural compounds act against proliferation and sustain the effects of cisplatin by cell cycle arrest, induction of apoptosis and amplification of P21 expression in tumor cells. In conclusion, using RSV or CRM as adjuvants in CisPt therapy might have a beneficial effect by supporting the effects induced by CisPt.

Cisplatin effect on head and neck squamous cell carcinoma cells is modulated by ERK1/2 protein kinases.

The extracellular signal-regulated kinases (ERKs) are key transducers of the extracellular signals into intracellular responses and represent major molecular players in tumorigenesis. The aim of this study was to determine how curcumin (CRM) used as an adjuvant supports the apoptotic process induced by a single chemical agent treatment (cisplatin-CisPT) on two head and neck squamous cell carcinoma cell lines (FaDu and PE/CA-PJ49) and the involvement of ERK1/2 and/or p53 activation in this process. Data have shown that the CisPt effect is potentiated by CRM. CRM induced an increase of p53 protein phosphorylation in both cell lines. CisPt decreased p53 protein phosphorylation in FaDu cells, but increased it in PE/CA-PJ49 cells. Data showed that the constitutive expression of activated ERK1/2 protein-kinase was different in the two analyzed tumor cell lines. ERK1/2 activation status was essential for both cell processes, proliferation and apoptosis induced by CisPt and/or CRM treatment on squamous cell carcinoma cells. Our data suggest that p53 phosphorylation in the apoptotic process induced by CRM treatment might require the involvement of ERK1/2. In this regard the CisPt treatment suggested that p53 phosphorylation is ERK1/2 independent in FaDu cells having a p53 gene deletion and ERK1/2 dependent in PE/CA-PJ49 cells having a p53 gene amplification. Moreover, in both tumor cell lines our results support the involvement of p53 phosphorylation-ERK1/2 activation-dependent in the apoptosis induced by combined treatments (CisPt and CRM). The use of CRM as adjuvant could increase the efficiency of chemotherapy by modulating cellular activation processes of ERK1/2 signaling pathways. In conclusion, the particular mode of intervention by which ERK1/2 might influence cell proliferation and/or apoptosis processes depends on the type of therapeutic agent, the cells' particularities, and the activation status of the ERK1/2.

Impact of early supplementation with low-dose aspirin on functional first trimester parameters in low-risk pregnancies.

INTRODUCTION: There is recent evidence that prophylaxis with 150 mg of aspirin given before 14-16 weeks significantly reduces preeclampsia rates and may improve pregnancy outcome. We conducted an observational study that investigates the effect of low-dose aspirin initiated early in pregnancy or in preconception on functional parameters assessed at 11-14 weeks. MATERIALS AND METHODS: We have retrospectively selected 128 pregnant women that presented for the first trimester screening for aneuploidies between 11+0 and 13+6 weeks of gestation and received low-dose aspirin before 14 weeks. We excluded cases with an estimated high risk for early preeclampsia (cut-off > 1:100). This group was matched to 1044 cases that did not receive aspirin in early pregnancy. We have selected for statistical analysis maternal parameters, ultrasound parameters (crown-rump length, nuchal translucency thickness, pulsatility index in uterine arteries - left, right, average and average uterine PI expressed in multiple of median (MoM)), first trimester maternal biochemical markers (free ß hCG and PAPP-A expressed in MoM), and the calculated risk for early onset and late onset preeclampsia. RESULTS: The most common dosages of aspirin were 75 mg (77 cases) and 100 mg (32 cases). The most significant results are within the aspirin group. In the subgroup that received aspirin before 11 weeks (110 cases), irrespective of the dosage, the uterine blood flow is significantly improved (average uterine PI 1.7 compared with 2.22, p < .05, (0.24-0.7) 95% CI) and the PAPP-A levels are higher (1.2 compared with 0.82, p > .05, [(-0.65) - 0.02] 95% CI). The estimated risk for both early and late onset preeclampsia in this group is reduced (1:2141 compared with 1:333 for early preeclampsia, p < .05, (1216-2398) 95% CI; 1:361 compared with 1:99 for late onset preeclampsia, p < .05, (173-351) 95% CI). CONCLUSION: Even though the results are not always statistically significant, they demonstrate that placentation parameters improve with higher doses of aspirin started before 11 weeks.