Gliomas are a group of primary brain tumors characterized by their aggressive nature and resistance to treatment. Infiltration of surrounding normal tissues limits surgical approaches, wide inter- and intratumor heterogeneity hinders the development of universal therapeutics, and the presence of the blood–brain barrier reduces the efficiency of their delivery. As a result, patients diagnosed with gliomas often face a poor prognosis and low survival rates. The spectrum of anti-glioma drugs used in clinical practice is quite narrow. Alkylating agents are often used as first-line therapy, but their effectiveness varies depending on the molecular subtypes of gliomas. This highlights the need for new, more effective therapeutic approaches. Standard drug-screening methods involve the use of two-dimensional cell cultures. However, these models cannot fully replicate the conditions present in real tumors, making it difficult to extrapolate the results to humans. We describe the advantages and disadvantages of existing glioma cell-based models designed to improve the situation and build future prospects to make drug discovery comprehensive and more effective for each patient according to personalized therapy paradigms.
C-type lectins (CTLs) are a large family of calcium-dependent carbohydrate-binding proteins that play crucial roles in innate immunity as pattern recognition receptors. Bivalve mollusks possess exceptionally diverse and expanded repertoires of CTLs, yet a systematic review integrating their structural, functional, and regulatory aspects has been lacking. This article provides a comprehensive synthesis of current knowledge on bivalve CTLs, analyzing their biosynthesis, complex tissue-specific expression under both normal and stressed conditions, and their multifaceted roles in immune defense and other physiological processes. Our analysis consolidates data on their diverse domain architectures, phylogenetic relationships, and the variability of key motifs within their carbohydrate-recognition domains. The results demonstrate that bivalve CTLs are not only critical for pathogen recognition, agglutination, and phagocytosis but also involved in processes like nutrition, development, byssus formation and biomineralization. However, a significant finding is that the detailed carbohydrate specificity for most bivalve CTLs remains poorly characterized, often limited to monosaccharide inhibition assays. In conclusion, while the immune role of bivalve CTLs is well-established, this review underscores a critical gap in understanding their fine glycan-binding profiles. Therefore, a shift in the focus of future research towards elucidating their structure and carbohydrate specificity is required for a full understanding of their biological functions and an assessment of their biomedical potential.
Gut microbes are important for saproxylophagous insects, but little is known about the specific types of microbes that we can grow in the lab and how their diet affects them. We characterized aerobic culturable microbes from the superworm Zophobas atratus larvae reared on a standard diet (SD) and a fungal-based diet (FD) using the selective plating and 16S rRNA sequencing of isolates. Five functional groups were cultured: amino acid autotrophs, enterobacteria, yeasts, cellulolytic bacteria, and molds. A quantitative assessment revealed distinct diet-dependent patterns: SD-fed larvae showed the dominance of enterobacteria and amino acid autotrophs, while FD-fed larvae exhibited a higher abundance of enterobacteria and yeasts. Mold populations remained minimal under both diets. A phylogenetic analysis of bacterial isolates showed four core bacterial phyla (Pseudomonadota, Actinobacteria, Bacillota, and Bacteroidota) with diet-sensitive genus-level variations. Pseudomonadota dominated both diets, but certain genera were associated with different diets: Micrococcus and Brucella in the SD versus Citrobacter and Pseudomonas in the FD. Shared genera (Klebsiella, Enterobacter, and Bacillus) may represent a core culturable community. These findings demonstrate the influence of diet on culturable gut microbes while highlighting the need for complementary molecular approaches to study unculturable taxa. The isolated strains provide resources for investigating microbial functions in insect nutrition.
Recently revised brain tumor classification suggested a glioma treatment strategy that takes into consideration molecular variants in IDH1 and TP53 marker genes. While pathogenic variants of IDH1 and TP53 can be accompanied by chromosomal instability (CIN), the impact of IDH1 and TP53 mutations on genome stability remains unstudied. Elevated CIN might provide therapeutic targets, based on synergistic effects of chemotherapy with CIN-inducing drugs. Using an assay based on human artificial chromosomes, we investigated the impact of common glioma missense mutations in IDH1 and TP53 on chromosome transmission and demonstrated that IDH1R132H and TP53R248Q variants elevate CIN. We next found enhanced CIN levels and the sensitivity of IDH1R132H/WT and TP53R248Q/R248Q genotypes, introduced into U87 MG glioma cells by CRISPR/Cas9, to different drugs, including conventional temozolomide. It was found that U87 MG cells carrying IDH1R132H/WT exhibit dramatic sensitivity to paclitaxel, which was independently confirmed on cell cultures derived from patients with naturally occurring IDH1R132H/WT. Overall, our results suggest that the development of CIN-enhancing therapy for glioma tumors with the IDH1R132H/WT genotype could be advantageous for adjuvant treatment.