Search Results (209)

Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article

Background: Breast cancer (BC) is highly heterogeneous, with varying molecular characteristics, such as reliance on autophagy. Autophagy is a critical cellular degradation process that helps cells survive under stress, but its regulation can be influenced by altered microRNA (miRNA) expression. Studying miRNA changes during starvation-induced autophagy in both mammary epithelial cells and BC cells could reveal potential molecular therapy targets. Methods: Rat mammary gland healthy epithelial and cancer cells were subjected to starvation, and differences in proliferation, migration, invasion, autophagy, and expression of autophagy-associated miRNAs were determined. Afterward, we assessed the effects of miR-218-5p modulation on the aforementioned processes. Results: Starvation-induced autophagy reduced the proliferation of all cells and increased the invasive and migratory capacity of cancer cells (p ≤ 0.05). We identified a miRNA signature related to starvation, comprising twenty-seven miRNAs. One miRNA had a significantly elevated baseline expression, while another six, including miR-218-5p, had a significantly lower basal expression in cancer cells compared to healthy cells (p ≤ 0.05). However, starvation caused significant miRNA expression changes, with miR-218-5p being upregulated specifically in cancer cells (p = 0.20–0.01). Functional studies on the role of miR-218-5p show that its inhibition decreases migration and leads to autophagosome accumulation. The study of miR-218-5p molecular targets has shown that its inhibition of sorting nexin 18 (SNX18) may act as an important regulator of the starvation-induced response in cancer cells. Conclusions: The baseline expression of miRNA related to starvation and autophagy differs between rat mammary gland cancer and healthy cells. The response to starvation also varies between cancer cells and normal cells. Starvation induces BC-specific miRNA dysregulation, affecting particularly miR-218-5p, which acts via SNX18, promoting the cancer cells’ survival. Full article

Pancreatic cancer cells exhibit a remarkable ability to tolerate nutrient deprivation, a phenomenon termed “austerity,” which enables their survival within the hypovascular tumor microenvironment. Conventional anticancer therapies frequently fail to effectively target these resilient neoplastic cells, posing a significant challenge to the therapeutic management of pancreatic cancer. Consequently, targeting austerity, the ability of cancer cells to tolerate nutrient starvation, represents a promising anti-austerity strategy for developing novel pancreatic cancer therapeutics. In this study, we investigated calliviminone A (CVM-A), a phloroglucinol–meroterpenoid isolated from Callistemon citrinus leaves, for its anti-austerity activity against PANC-1 human pancreatic cancer cells. Calliviminone A exhibited potent preferential cytotoxicity in nutrient-deprived medium (NDM) with a PC₅₀ of 0.57 µM, while showing minimal toxicity in nutrient-rich Dulbecco’s Modified Eagle’s medium (IC₅₀ = 45.2 µM), indicating a favorable therapeutic index. Real-time live-cell imaging revealed that CVM-A induced significant morphological changes, including cell shrinkage and membrane blebbing, leading to cell death within 24 h of NDM. Furthermore, under normal nutrient conditions in Dulbecco’s Modified Eagle’s Medium (DMEM), CVM-A significantly inhibited PANC-1 cell migration (up to 47% reduction at 20 µM) and colony formation (over 80% suppression at 25 µM), suggesting its antimetastatic potential. Western blot studies demonstrated that CVM-A downregulated key survival components of the PI3K/Akt/mTOR signaling pathway, completely inhibiting Akt and p-Akt at 2.5 µM in NDM, and suppressing insulin-induced Akt activation. These findings highlight CVM-A as a promising lead compound for developing novel anticancer therapies that target the adaptive survival mechanisms and metastatic potential of pancreatic cancer in nutrient-deprived microenvironments. Full article

Respiration rates in insects are critical for survival and environmental adaptation, being influenced by developmental stages, environmental conditions, and the regulation of mitochondrial protein-coding genes. However, methods for field-based measurements in small-sized insects remain limited. In this study, we established a portable photosynthesis system to quantify respiration rates in five small-sized insects (body length < 8 mm): Acyrthosiphon pisum, Aphis citricidus, Tuta absoluta, Tribolium castaneum, and Bactrocera dorsalis. We tested its effectiveness across life stages and under diverse treatments, including light/dark cycles, insecticides, temperature shifts, starvation, mitochondrial inhibitors, and RNA interference. The system exhibited high sensitivity and reproducibility rates, revealing stage-specific respiration patterns. Various treatments, as well as expression changes in mitochondrial protein-coding genes, significantly affected respiration rates. This study validates the portable system as a reliable tool for insect respiration studies and highlights regulatory networks associated with respiratory plasticity. These findings enhance experimental methodologies and advance our understanding of insect adaptation to environmental stressors and pest control strategies. Full article

Candida auris is a multidrug-resistant pathogen with a high mortality rate and widespread distribution. Additionally, it can persist on inert surfaces for extended periods, facilitating its transmissibility in hospital settings. Autophagy is a crucial cellular mechanism that enables fungal survival under adverse conditions. A fundamental part of this process is mediated by vacuolar proteases, which play an essential role in the degradation and recycling of cellular components. The present work explores the relationship between C. auris vacuolar peptidases and autophagy, aiming to establish a precedent for understanding the survival mechanisms of this emerging fungus. Thus, eight genes encoding putative vacuolar peptidases in the C. auris genomes were identified: PEP4, PRB1, PRC1, ATG42, CPS, LAP4, APE3, and DAP2. Analysis of the protein domains and their phylogenetic relationships suggests that these enzymes are orthologs of Saccharomyces cerevisiae vacuolar peptidases. Notably, both vacuolar protease gene expression and the proteolytic activity of cell-free extracts increased under nutritional stress and rapamycin. An increase in the expression of the ATG8 gene and the presence of autophagic bodies were also observed. These results suggest that proteases could play a role in yeast autophagy and survival during starvation conditions. Full article

To accurately detect internal and environmental cues, bacteria have evolved signal transduction pathways such as two-component systems (TCSs) to reprogram appropriate genetic and physiological functions for adaptation and survival. The MprAB TCS is commonly found in actinobacteria and has been associated with important processes such as mycobacterial virulence, nutrient starvation, and environmental stress, particularly cell envelope stress. However, a comprehensive investigation of the function and response network of the MprAB TCS in corynebacteria remains to be carried out. In this study, we report that the MprAB TCS (previously named CgtSR2) plays a critical role in regulating genes involved in cell envelope remodeling in C. glutamicum. The results indicated that the MprAB TCS directly controls a broad regulon, including cell wall biosynthesis proteins, alternative sigma factors, secreted proteins of unknown function, and the mprAB gene locus itself. Among these, the HtrA-like serine protease confers vancomycin and penicillin resistance. Furthermore, we found that the function of the cell envelope was disrupted during overexpression of mprA, resulting in elongated cell morphology and increased cell membrane permeability, as well as enhanced excretion of L-alanine. In conclusion, our findings provide novel insights into how the conserved MprAB TCS controls cell envelope homeostasis in distant actinobacteria. Full article

In drylands, microalgae dwelling in the biocrust are inevitably confronted with nitrogen deficiency and desiccation stress, despite the protection afforded by the soil biological complex. However, the environmental adaptive features and mechanisms of these microalgae remain largely unknown. In this study, we explored the adaptive changes of a biocrust-derived unicellular microalga, Vischeria sp. WL1 (Eustigmatophyceae), in the face of long-term nitrogen deficiency. Attention was focused on the alterations in cell wall properties and the associated desiccation resistance. After exposure to long-term nitrogen deficiency, the cell walls of Vischeria sp. WL1 thickened substantially, accompanied by enhanced rigidity and an improvement in desiccation resistance. In contrast, Vischeria sp. WL1 cells cultivated under nitrogen-replete conditions were highly vulnerable to desiccation stress. Additional cell wall alterations after nitrogen starvation included distinct surface sculpturing, variations in monosaccharide composition, and changes in functional groups. Collectively, this study provides valuable insights into the survival strategies of biocrust-derived microalgae in nitrogen-deficient dryland environments. Full article

Insects often encounter starvation stress, especially during invasion spread or population outbreaks. The fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), is an important invasive pest in China, and the starvation resistance of its larvae determines population spread and resulting outbreak threat. In this study, we investigated the starvation resistance of H. cunea larvae and the effects of starvation stress on their life history and adult fitness. Larval starvation resistance increased along with the instar stage, and the second-day sixth instar molt was critical for starvation resistance. The response to starvation stress was reflected in multiple biological indicators observed in H. cunea. Complete food deprivation reduced the pupation survival rate of sixth instar larvae, prolonged their developmental duration, reduced pupal and adult body mass, shortened adult forewing length and lifespan, and reduced female egg production. The sixth instar larvae showed a certain ability to recover after refeeding. However, negative impacts of the starvation period on larval life history traits, such as pupation survival rate, pupal and adult body mass, adult longevity, and fecundity, were still observed even after refeeding, and the effects of refeeding were affected by larval starvation duration and refeeding mode. These results suggested that H. cunea larvae were highly resistant to starvation, that starvation stress negatively affected their larval life history and adult fitness, and that the pattern of the effects of post-starvation refeeding on larval and adult fitness was related to the duration of starvation and the refeeding mode. The results of this study offer important insights into understanding the physiological response mechanisms of invasive insects under starvation stress. Full article

Background/Objectives: Non-replicating persisters (NRPs) of Mycobacterium abscessus are a bacterial subpopulation that can survive in the host under unfavorable conditions, such as hypoxia or nutrient starvation. The eradication of these bacteria is difficult, which is one reason for the long treatment duration and treatment failure. The drug discovery process should therefore contain methods to screen activity against NRPs. Methods: A hypoxic environment is used to generate NRPs of M. abscessus that are termed low-oxygen persisters (LOPs). For this, an oxidation process is used to transition a replicating culture of M. abscessus distributed in microtiter plates within a sealable box into LOPs. Colony counting, automated object counting, bactericidal activity determination of known agents, and confocal laser scanning microscopy are used to study the obtained culture. Results: The obtained culture shows typical attributes of non-replicating cells, such as significantly reduced replication, the reversibility of the LOP state under aerobic conditions, delayed regrowth on solid medium, altered morphological patterns on a single-cell level, and phenotypical resistance against a variety of clinically relevant antimycobacterial compounds. The study reveals metronidazole and niclosamide as bactericidal against M. abscessus LOPs. These compounds can be used as LOP verification compounds within the described model. Conclusions: Our model is easily implemented and quickly identifies compounds that are inactive under hypoxic conditions. It can therefore accelerate the identification of clinically effective antimycobacterial drug substances, and can be a helpful tool during the drug development process. Full article

Conventional cancer treatments often have complications and serious side effects, with limited improvements in 5-year survival and quality of life. Photothermal therapy (PTT) employs materials that convert light to heat when exposed to near-infrared light to raise the temperature of the tumor site to directly ablate tumor cells, induce immunogenic cell death, and improve the tumor microenvironment. This therapy has several benefits, including minimal invasiveness, high efficacy, reduced side effects, and robust targeting capabilities. Beyond just photothermal conversion materials, nanoplatforms significantly contribute to PTT by supplying effective photothermal conversion materials and bolstering tumor targeting to amplify anti-tumor effects. However, the anti-tumor effects of PTT alone are ultimately limited and often need to be combined with other therapies. This narrative review describes the recent progress of PTT combined with chemotherapy, radiotherapy, photodynamic therapy, immunotherapy, gene therapy, gas therapy, chemodynamic therapy, photoacoustic imaging, starvation therapy, and multimodal therapy. Studies have shown that combining PTT with other treatments can improve efficacy, reduce side effects, and overcome drug resistance. Despite the encouraging results, challenges such as optimizing treatment protocols, addressing tumor heterogeneity, and overcoming biological barriers remain. This paper highlights the potential for personalized, multimodal approaches to improve cancer treatment outcomes. Full article

The ability to survive starvation is a critical evolutionary adaptation, yet the molecular mechanisms underlying this capability remain incompletely understood. Pore-forming proteins (PFPs) are typically associated with immune defense, where they disturb the membranes of target cells. However, the role of PFPs in non-immune functions, particularly in metabolic and structural adaptations to starvation, is less explored. Here, we investigate the aerolysin-like PFP LIN-24 in Caenorhabditis elegans and uncover its novel function in enhancing starvation resistance. We found that LIN-24 expression is upregulated during starvation, leading to increased expression of the lipase-encoding gene lipl-3. This upregulation accelerates the mobilization and degradation of lipid stores, thereby sustaining energy levels. Additionally, LIN-24 overexpression significantly preserves muscle integrity, as evidenced by the maintenance of muscle structure compared to wild-type worms. Furthermore, we demonstrate that LIN-24 induces the formation of donut-shaped mitochondria, a structural change likely aimed at reducing ATP production to conserve energy during prolonged nutrient deprivation. This mitochondrial remodeling depends on genes involved in mitochondrial dynamics, including mff-1, mff-2, drp-1, and clk-1. Collectively, these findings expand our understanding of PFPs, demonstrating their multifaceted role in stress resistance beyond immune defense. LIN-24’s involvement in regulating metabolism, preserving muscle structure, and remodeling mitochondria highlights its crucial role in the adaptive response to starvation, offering novel insights into the evolution of stress resistance mechanisms and potential therapeutic targets for conditions related to muscle preservation and metabolic regulation. Full article

Ticks are hematophagous ectoparasites that transmit pathogens and inflict significant economic losses on the cattle industry. Remarkably, they can survive extended periods of starvation in the absence of a host. The primary objective of this study was to investigate the metabolic adaptations that enable the tick Rhipicephalus microplus to endure starvation using the BME26 cell line as a model system. To simulate nutrient deprivation, cells were subjected to starvation conditions by replacing the L-15 culture medium with phosphate-buffered saline (PBS). Our findings show that these tick cells can endure experimental starvation for up to 48 h. The assessment of glycogen levels in starved cells shows a significant decrease, at both the 24 h and 48 h marks. Additionally, upregulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression, along with downregulation of hexokinase (HK) and pyruvate kinase (PK) gene expression, indicated that BME26 cells would prioritize the gluconeogenic pathway over the glycolytic pathway under starvation conditions. Moreover, the transcriptional levels of autophagy-related genes (ATG) were upregulated in response to starvation. Taken together, our findings suggest a potential role for autophagy in supplying substrates for the gluconeogenic pathway in nutrient-deprived tick cells. This work contributes to the understanding of metabolic regulation in R. microplus ticks and offers valuable insights for tick control strategies. Full article

The appetite of honeybees for food is crucial to their survival and reproduction, as they sustain their entire colony by collecting pollen and nectar for nutrients. Dopamine, an important neurotransmitter, regulates appetite and satiety. However, how dopamine regulates honeybee foraging behavior remains unexplored. In this study, we investigated dopamine expression in 23-day-old Apis mellifera under different food-wanting conditions and identified differentially expressed genes (DEGs) in the brains of honeybees using RNA sequencing technology. We showed that dopamine levels in honeybees starved for 2 h were higher than those sated after 2 h of starvation. RNA-seq results revealed there were differences in the expression of cytochrome P450-dependent monooxygenase (CYP9Q1) in honeybees, which regulated the sucrose sensitivity of honeybees under different intake states. Furthermore, CYP9Q1 targeted the expression of the insulin receptor substrate (IRS) to promote dopamine synthesis. Our findings emphasize the relationship between dopamine and honeybees’ desire for food at the molecular level, providing a reference for further exploring the mechanism of food wanting. Full article

We investigated the effect of feed deprivation for 45 days on the growth, immunity, and health of 0⁺marron (Cherax cainii) initially fed for 110 days on various protein sources including fishmeal (FM), poultry by-product meal (PBM), black soldier fly meal (BSFM), soybean meal (SBM), lupin meal (LM), and tuna hydrolysate. The marron were weighed and sacrificed immediately after feeding stopped (day 0) and at days 15, 30, and 45 after the feed deprivation trial commenced. Total haemolymph count, differential haemocyte count, lysozyme activity, protease activity, total bacterial count in the digestive tract, and organosomatic indices were analysed. Initially feeding marron any protein sources did not influence the percentage of weight gain and specific growth rates of marron. All marron showed more than 83% survival; however, marron fed soybean meal showed significantly lower survival than others. Dietary sources of protein altered organosomatic indices of starved marron during various starvation periods and resulted in a significant decrease in total haemocyte counts, lysozyme activity, protease activity, and bacterial count in the digestive tract of marron. Starved marron initially fed PBM and BSFM showed higher tolerance to starvation, followed by marron initially fed FM and SBM, while marron initially fed TH and LM showed the highest susceptibility to starvation. Full article

This research investigated the inhibition of *Escherichia coli* ATCC 25922 (E. coli) bacterial growth in situ, specifically on the stems and aerial parts of *Agastache mexicana* subsp. mexicana (Amm) or “purple toronjil” and on food-grade paper, both contained within Kraft paper bags with a plastic window. The qualitative phytochemical profile of an aqueous extract of Amm revealed the presence of various compounds including alkaloids, coumarins, tannins, flavonoids, saponins, triterpenes, and sterols. The results indicate that these secondary metabolites exhibit a synergistic bactericidal effect, especially when combined with temperature and starvation stress. This was quantified using a decay equation referred to as the bacterial growth inhibition profile of E. coli (BGIPEc). Calculations, which included first derivatives, gradients based on substrate effects and temperature as well as the area under the curve of BGIPEc, demonstrated that higher temperatures led to the greater inhibition of colony forming units (CFUs), further enhanced by the presence of secondary metabolites. Additionally, a shorter half-life corresponded to a faster change rate and a lower area under the curve, indicating a reduced survival rate over time. At lower temperatures, E. coli exhibited a survival effect, which was corroborated by the preceding calculations. Full article