Frontiers in bioscience (Elite edition)最新文献

The brain malignant tumor Glioblastoma multiforme (GBM) has a median survival of 14-16 months using current treatments; thus, understanding the pathology of GBM is crucial for proposing new therapies and increasing overall survival outcomes. Therefore, this study aimed to analyze different elements, particularly growth factors and the related signal transduction pathways, which play a role in brain neoplastic development, from stem cells to established solid brain tumors, and the application of current immunology techniques, molecular biology, and nanotechnology. Targeting growth factors, especially insulin-like growth factor-1 (IGF-I) (the principal neoplastic development factor) using anti-gene technologies-antisense and triple helix-has previously been shown to produce an immune anti-tumor response (CD8, CD28) through the TK/PI3K/AKT pathway. This immune response was increased using phytochemicals (phenolics), especially nanoparticles (theranostic nanoparticles), by modulating IGF-I through common pathways (IGF-I-R and TK/PI3K/AKT/TLR/MAPK and JAK/STAT). This review demonstrates how studies on central nervous system neoplastic development progressively led to establishing clinical cancer gene therapies, increasing GBM survival by 20-24 months. The presented studies compare the results of cancer gene therapy with other current immunotherapies. Moreover, this research chapter briefly describes the investigations of nanotechnology related to neurotumorigenesis and GBM therapies. The presented studies relate to nanotechnology and compare the results of cancer gene therapy with other current immunotherapies.

Background: Fanconi anemia (FA) is an inherited genetic instability syndrome that increases the risk of developing head and neck squamous cell carcinoma, particularly in the oral cavity. These epithelial cancers often arise from visible oral and potentially malignant disorders (OPMD). Research has shown that oral brush biopsies combined with cytology, such as manual DNA cytometry, can facilitate the early detection of OPMDs that require treatment. Thus, this study aimed to evaluate the diagnostic accuracy of a DNA karyometry (DNA-KM) system in the brush biopsy-based diagnostic workup for OPMDs with FA.

Methods: Feulgen-stained liquid-based oral smears were included from 327 independent OPMD cases, which had available cytological diagnoses and clinicopathological reference standards. These samples were automatically analyzed using a DNA-KM system (MotiCyte-auto), which employs digital nuclear classifiers based on expert classification of nuclear images and machine learning algorithms.

Results: The detection of (suspected) DNA stemline aneuploidy or single-cell aneuploidy with DNA-KM demonstrated a sensitivity of 69% and a specificity of 96%. In our analysis, when DNA-KM was combined with cytology, we observed a sensitivity of 75% and a specificity of 96%. Meanwhile, additional research using the variation coefficient of a "broad-based" peritetraploid stemline (BPS) as an alternative algorithm further increased the sensitivity to 84%. However, employing this algorithm slightly decreased specificity to 92% at a cut-off of 5.83.

Conclusions: Artificial intelligence (AI)-assisted DNA-KM, with automated slide-scanning and digital classification of nuclei, can serve as a valuable additional method in the brush biopsy-based cytological diagnosis of OPMD in FA. This approach can help identify lesions that require clinical intervention.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder with which the leucine-Rich repeat kinase 2 glycine 2019 serine (LRRK2 G2019S) mutation is strongly associated. This mutation elevates kinase activity, disrupts mitochondrial function, increases reactive oxygen species (ROS) production, and impairs DNA repair mechanisms, all of which contribute to the pathogenesis of PD. Thus, addressing these pathological features through targeted delivery systems holds promise for more effective therapies.

Methods: This study aimed to investigate the use of Ginkgo biloba leaf extract (EGB) to synthesize sphingomyelin-cholesterol solid lipid nanoparticles (SLNPs) functionalized with poly-L-lysine (EGB-PLL-SLNPs) for siRNA delivery targeting the LRRK2 G2019S mutation. SLNPs suspended in water (H₂O-PLL-SLNPs) served as the comparator. In vitro assays were conducted using either wild-type or LRRK2 G2019S-transformed SH-SY5Y and HEK293 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to evaluate the cytotoxicity of the SLNPs and nanocomplexes; meanwhile, flow cytometry was used to assess caspase 3/7 activity, mitochondrial membrane potential, DNA damage, and ROS levels.

Results: Treatment with EGB-PLL-SLNPs significantly improved mitochondrial health, reducing depolarized and dead cells and enhancing overall cell viability. ROS levels, DNA damage and kinase activity were significantly decreased compared to the control H₂O-PLL-SLNPs.

Conclusion: The enhanced therapeutic outcomes observed with the EGB-PLL-SLNPs can be attributed to the bioactive compounds in EGB, particularly the flavonoids and terpenoids, such as quercetin and kaempferol. These molecules play crucial roles in stabilizing mitochondrial membranes, facilitating ATP synthesis, and regulating genes linked to mitochondrial biogenesis. The interaction between EGB and siRNA to mediate gene silencing provides a multifaceted approach to counteracting PD pathophysiology. This study demonstrates that EGB-PLL-SLNPs offer superior gene silencing and cytoprotective effects compared to conventional formulations. The integration of plant-based bioactives with nanomedicine enhances therapeutic delivery and efficacy, positioning biosynthesized PLL-SLNPs as a promising strategy for treating Parkinson's disease.

Coccinia grandis (L.) Voigt (ivy gourd) is popularly consumed in South Asia for food and therapeutic purposes. C. grandis acts as a remedy for various ailments, such as hypertension, diabetes, cancer, ulcers, diarrhea, jaundice, inflammation, fever, bronchitis, burns, skin eruptions, insect bites, allergies, eye infections, and urinary disorders. Researchers have identified phytoconstituents in diverse chemical classes from this species, including alkaloids, flavonoids, coumarins, esters, ethers, fatty acids, fatty alcohols, terpenoids, and phenolic compounds. Comprehensive research conducted in vitro and in vivo has confirmed the properties of the plant as antidiabetic, anticancer, antiparasitic, antimicrobial, hepatoprotective, analgesic, antipyretic, anti-Alzheimer's, anticataract, antileishmanial, anti-anaphylactic, anti-histaminic, and wound-healing agent, as well as being advantageous for cardiovascular health. Most pharmacological findings are derived from studies on the extracts and the subsequent phytoconstituents from this plant species. Nevertheless, the specific phytoconstituents underlying these biological effects and the mechanisms of action involved are yet to be fully identified. Toxicological evaluations indicate that C. grandis is generally safe, although high doses can cause dose-dependent hepatotoxicity. Moreover, the clinical trials focusing on the antidiabetic effects of C. grandis demonstrate promising effects in managing glucose dysregulation. This review aims to provide a comprehensive update on C. grandis, expanding on previous studies by incorporating a broader ethnomedicinal scope, a more extensive phytochemical profile with detailed chemical structures, and additional clinical trial data. Unlike prior publications, this review emphasizes C. grandis as a functional food, highlighting its potential in chronic disease management. By integrating these aspects, this study offers a more in-depth analysis of the therapeutic potential and future applications of this plant. The functional food aspect of C. grandis, rich in bioactive compounds, supports its role in preventing and managing chronic diseases as a regular vegetable.

Biological therapies have transformed cancer treatment by targeting the molecular mechanisms involved in carcinogenesis. However, higher costs, limited accessibility, and supply chain disruptions-such as those caused by COVID-19 in recent years-underscore the need for cost-effective alternatives. Biosimilars, which are drugs that are highly similar to their reference biologics in terms of safety, efficacy, and quality, offer a viable solution (as these demonstrate clinically meaningful outcomes). This review article examines the role of biosimilars, mainly in gynecological cancers. The primary focus of this article is to compare the efficacy, safety, and cost-effectiveness of biosimilars, as well as to explore the barriers that restrict their widespread adoption. A comprehensive literature review was conducted, analyzing various studies, regulatory guidelines, and the latest data on biosimilars for the treatment of gynecological cancers. Pivotal trials, such as the GOG-0218, ICON7, and RUBY, were reviewed to assess the efficacy, safety, and cost-effectiveness of these biosimilars. This review highlights key oncologic therapies, including bevacizumab, trastuzumab, pembrolizumab, and their biosimilars, mainly for gynecological cancers. Additionally, this review considers the challenges of immunogenicity, interchangeability, and clinician awareness. After reviewing the latest peer-reviewed literature and related online materials, we found that biosimilars demonstrate comparable efficacy and safety to their reference biologics while also being more cost-effective. Recent clinical trials support the role of biosimilars in limiting the progression of disease and improving overall survival while reducing the financial burden of cancer treatments.

Background: This study aimed to investigate the modeling and design of product compositions using grape stem extracts, with an emphasis on phenolic compounds and antioxidant activity. Grape stems, a significant byproduct of winemaking, are a rich source of bioactive phenolic substances.

Methods: Aqueous ethanol extracts were obtained from grape stems of European varieties; the Magarach Institute developed a new selection. Phenolic compounds were quantified using ultraviolet-visible spectrophotometry via the Folin-Ciocalteu method and high-performance liquid chromatography (HPLC). Antioxidant activity was evaluated using an amperometric method. In addition, mathematical models have been developed to predict product composition based on mixing various components. Key HPLC parameters (detection wavelength, flow rate, column temperature, injection volume) and amperometric calibration procedures are described.

Results: The mass concentration of phenolic substances in the extracts ranged from 7.95 to 16.40 g/dm³, and the antioxidant activity ranged from 6.30 to 13.90 g/dm³. Identifying the compositions of stem extracts was conducted with a focus on studying substances with a non-flavonoid structure: phenolic acids, esters, and stilbenes. Statistical analysis (analysis of variance (ANOVA) with post-hoc t-tests) confirmed significant differences (p < 0.05) between grape varieties. Furthermore, the developed mathematical model-validated using coefficient of determination (R²) and Root Mean Squared Error (RMSE) metrics-demonstrated robust predictive capabilities for product compositions.

Conclusions: These results indicate that grape stems are a valuable source of bioactive compounds for developing functional products. In addition, the proposed mathematical modeling approach offers a reliable method for designing product compositions. These findings provide a basis for developing software tools to optimize product formulation in the food industry.

Background: The E. coli O157:H7 strain has been the subject of many studies. In addition to producing severe abdominal illness in humans and animals, the E. coli O157:H7 strain is characterized by the production of Shiga toxins and demonstrates resistance to multiple antibiotics.

Methods: In this study, 20 fecal samples from patients with typical symptoms of E. coli O157:H7 infection and 20 from animals that tested positive for the same pathogen were analyzed. The bacterium was isolated, identified, and classified using both culture-based and molecular methods, employing the rpoB, stx, waa, and waaO genes.

Results: The E. coli O157:H7 strain classification was highly similar to the E. coli O157:H7 strain Sakai. The rpoB, stx, waa, and waaO genes were deposited on the NCBI website under accession numbers PP059841, OR939814, PP059843, and PP059842, respectively. The mutant sequences at the waa sites K, L, and Y were analyzed to determine the alterations in the associated gene function, cell wall formation, and the ability of the mutant E. coli O157:H7 to develop antibiotic resistance compared to the wild-type.

Conclusions: Antibiotic resistance in the mutant E. coli O157:H7 increased significantly regarding some type of theses antimicrobial agents, while in some cases it decreased. This depends on the type of antibiotics and its mode of action and target. This may be explained by the waaK and waaL genes, which prevent the entry of antimicrobial agents into the bacterial cell.

Background: The unsafe disposal of milk processing effluents has a negative impact on the environment due to their high content of nutrients and organic matter. Green alternatives can be applied to effectively manage and valorize these effluents, reducing their environmental footprint.

Methods: The ability of the free-living cyanobacterium Oscillatoria sp. to grow in real cheese whey was evaluated as a potential strategy for integrating dairy wastewater treatment with biomass valorization. Autotrophic and mixotrophic cultures were maintained under controlled laboratory conditions and monitored over 28 days for growth, cell viability, biomass, pigment content, and physicochemical parameters, including pH, protein, carbohydrate, and chemical oxygen demand (COD).

Results: Oscillatoria sp. successfully adapted to the initial acidic conditions of the effluent (pH 2.8-2.9), increasing the pH of the treated whey to levels suitable for industrial wastewater disposal (pH 6.0-9.0). A 5-fold increase in dehydrogenase activity was observed after a 28-day culture, with no signs of oxidative damage. Cyanobacterial biomass cultivated under mixotrophic conditions displayed a significant reduction (∼55%) in photosynthetic pigments, including chlorophyll a and total carotenoids, compared to autotrophic cultures. Notably, Oscillatoria sp. biomass increased by 2.3-fold under mixotrophy, compared to the autotrophic control. The higher biomass production was accompanied by a significant reduction in the whey COD from 35,250 mg/L to 8500 mg/L, along with a 65% and 80% decrease in protein and carbohydrate content, respectively.

Conclusions: These findings provide new insights into the metabolic behavior of Oscillatoria sp. during cheese whey bioremediation, highlighting the potential of mixotrophic cyanobacteria for managing dairy wastewater management.

Healthcare-associated infections (HAIs) are a source of constant risk for inpatients and healthcare workers and a serious challenge to human health services worldwide. Common surfaces, such as doorknobs, tables, and bedrails, can become contaminated and develop into a reservoir of pathogens; thus, common surfaces can play an important role in the fomite-mediated pathway through which HAIs are transmitted. Non-critical disinfection techniques are common practice in the nosocomial setting, aiming to reduce the bioburden of common surfaces and prevent the spread of HAIs. However, these techniques are limited by factors such as the need for frequent disinfectant reapplication and the potential recontamination that can occur at any moment after cleaning. Light-activated antimicrobial nanocoatings are an interesting alternative to overcome these issues, since these nanocoatings can confer self-disinfection capacities to nosocomial common surfaces, to supplement non-critical disinfection. Thus, this review aims to discuss the relevance of fomites and gaps in common disinfection strategies that favor the propagation of HAIs. In addition, nanotechnology-based antimicrobial coatings are considered, along with strategies for nanoparticle-based antimicrobial coating development. Furthermore, the use of titanium oxide nanoparticles to formulate photo-responsive antimicrobial nanocomposites/nanocoatings and concerns related to toxicity, environmental fate, and bacterial resistance development are discussed. Finally, emerging photo-responsive antimicrobial nanotechnologies and future perspectives are considered.

The contamination of soil with toxic heavy metals is considered a significant environmental concerns, with the problem intensifying rapidly due to shifts in industrial practices. Even in trace quantities, heavy metals and metalloids, such as chromium, lead, mercury, cadmium and arsenic, are toxic and carcinogenic, representing a significant threat to agricultural production and human health. Additionally, prolonged exposure to these heavy metals can cause adverse health effects in humans and other living organisms. Heavy metals are non-degradable and tend to accumulate in soil, meaning their removal is necessary. One of the more sophisticated techniques for the remediation of heavy metals is utilizing biological methods, which employ naturally occurring microorganisms, such as Pseudomonas. Bioremediation is a superior method for the elimination of heavy metals in comparison to other approaches due to its environmentally benign nature, economic viability, and minimal labor and effort requirements, bioremediation is a superior method for the elimination of heavy metals in comparison to other approaches. Pseudomonas species can absorb heavy metals from soil and utilize these toxic contaminants in their metabolic processes, or transforming them into less or non-toxic forms. This review is focused on the studies that used the Pseudomonas genus is utilized for heavy metal bioremediation in contaminated soil. Notably, applying this strategy as a sustainable environmental technology in the near future has shown synergistic benefits with marked-fold increases in removing heavy metals from soil.