Destroying pathogen-tumor symbionts synergizing with catalytic therapy of colorectal cancer by biomimetic protein-supported single-atom nanozyme

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 21, 2023

The crucial role of intratumoral bacteria in the progression cancer has been gradually recognized with development sequencing technology. Several which have identified as pathogens that induce progression, metastasis, and poor outcome cancer, while tumor vascular networks immunosuppressive microenvironment provide shelters for localization. Thus, mutually-beneficial interplay between tumors, named "pathogen-tumor symbionts", is probably a potential therapeutic site treatment. Herein, we proposed destroying pathogen-tumor symbionts strategy kills pathogens, F. nucleatum, to break symbiont synergize kill colorectal (CRC) cells. This was achieved by groundbreaking protein-supported copper single-atom nanozyme (BSA-Cu SAN) inspired structures native enzymes are based on protein, metal elements active center. BSA-Cu SAN can exert catalytic therapy generating reactive oxygen species (ROS) depleting GSH. vitro vivo experiments demonstrate passively targets sites efficiently scavenges nucleatum situ destroy symbionts. As result, ROS resistance CRC through elevated autophagy mediated relieved, contributing apoptosis cells induced intracellular redox imbalance generated SAN. Particularly, experiences renal clearance, avoiding long-term systemic toxicity. work provides feasible paradigm block antitumor an optimized trail clearable

Language: Английский

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The Role of the Microbiome in the Etiopathogenesis of Colon Cancer

Annual Review of Physiology, Journal Year: 2024, Volume and Issue: 86(1), P. 453 - 478

Published: Feb. 12, 2024

Studies in preclinical models support that the gut microbiota play a critical role development and progression of colorectal cancer (CRC). Specific microbial species their corresponding virulence factors or associated small molecules can contribute to CRC either via direct effects on neoplastic transformation epithelial cells through interactions with host immune system. Induction DNA damage, activation Wnt/β-catenin NF-κB proinflammatory pathways, alteration nutrient's availability metabolic activity are main mechanisms by which CRC. Within tumor microenvironment, alter recruitment, activation, function various cells, such as T macrophages, dendritic cells. Additionally, shape composition cancer-associated fibroblasts extracellular matrix components, fashioning an immunosuppressive pro-tumorigenic niche for Understanding complex interplay between tumorigenesis provide therapeutic opportunities prevention treatment

Language: Английский

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Gut microbiome-metabolites axis: A friend or foe to colorectal cancer progression

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116410 - 116410

Published: March 9, 2024

An expanding corpus of research robustly substantiates the complex interrelation between gut microbiota and onset, progression, metastasis colorectal cancer. Investigations in both animal models human subjects have consistently underscored role bacteria a variety metabolic activities, driven by dietary intake. These activities include amino acid metabolism, carbohydrate fermentation, generation regulation bile acids. derivatives, turn, been identified as significant contributors to progression This thorough review meticulously explores dynamic interaction metabolites derived from breakdown acids, fatty synthesis. Notably, acids recognized for their potential carcinogenic properties, which may expedite tumor development. Extensive has revealed reciprocal influence on intricate spectrum cancer pathologies. Furthermore, strategies modulate microbiota, such modifications or probiotic supplementation, offer promising avenues prevention adjunctive treatment Nevertheless, additional is imperative corroborate these findings enhance our comprehension underlying mechanisms

Language: Английский

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An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 8, 2024

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, impact microbiota on initiation cancer is becoming increasingly evident, influencing tumor microenvironment (TME) for both local distant tumors. Moreover, it even suggested to play a significant role process immunotherapy, contributing high specificity therapeutic outcomes long-term effectiveness across various types. Probiotics, with their generally positive influence microbiota, may serve as effective agents synergizing immunotherapy. They crucial activating immune system inhibit growth. In summary, this comprehensive review aims provide valuable insights into dynamic interactions between probiotics, cancer. Furthermore, we highlight recent advances mechanisms using probiotics improve By understanding these complex relationships, unlock innovative approaches diagnosis treatment while optimizing effects

Language: Английский

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Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 9, 2024

Colorectal cancer (CRC) is a significant global health burden, with high morbidity and mortality rates. It often diagnosed at middle to advanced stage, affecting approximately 35% of patients the time diagnosis. Currently, chemotherapy has been used improve patient prognosis increase overall survival. However, can also have cytotoxic effects lead adverse reactions, such as inhibiting bone marrow hematopoiesis, causing digestive dysfunction, hand-foot syndrome, even life-threatening conditions. In response these effects, researchers proposed using Traditional Chinese Medicine (TCM) an option treat cancer. TCM research focuses on prescriptions, herbs, components, which form essential components current in medicine. The study implementation prescriptions herbs demonstrate its distinctive holistic approach therapy, characterized by applying multi-component multi-target treatment. TMC advantages developing new drugs they consist single ingredients, require smaller medication dosages, precise measure pharmacodynamic clear mechanism action compared herbs. further still needed determine whether fully substitute therapeutic efficacy prescriptions. This paper presents comprehensive analysis advancements made components. findings this serve theoretical basis for who are interested exploring potential treatment colorectal

Language: Английский

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Gut microbes on the risk of advanced adenomas

BMC Microbiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 18, 2024

Abstract Background More than 90% of colorectal cancer (CRC) arises from advanced adenomas (AA) and gut microbes are closely associated with the initiation progression both AA CRC. Objective To analyze characteristic in AA. Methods Fecal samples were collected 92 184 negative control (NC). Illumina HiSeq X sequencing platform was used for high-throughput microbial populations. The results annotated compared NCBI RefSeq database to find characteristics R-vegan package α diversity β diversity. included box diagram, Principal Component Analysis (PCA), principal co-ordinates analysis (PCoA), non-metric multidimensional scaling (NMDS). risk prediction models constructed based on six kinds machine learning algorithms. In addition, unsupervised clustering methods classify bacteria viruses. Finally, viruses different subtypes analyzed. Results abundance Prevotella sp900557255 , Alistipes putredinis Megamonas funiformis higher AA, while Lilyvirus Felixounavirus Drulisvirus also Catboost model predicting has highest accuracy (bacteria test set: 87.27%; virus 83.33%). 4 (B1V1, B1V2, B2V1, B2V2) distinguished enteroviruses (EVs). Escherichia coli D CAG-180 sp000432435 Phocaeicola plebeiuA Teseptimavirus Svunavirus Jiaodavirus subtypes. indicated that improved after incorporating discovery sets 100%, 96.34%, 98.46% subtypes, respectively. Conclusion have high value early warning As promising non-invasive biomarkers, can become potential diagnostic targets be by typing.

Language: Английский

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Virulence factor discovery identifies associations between the Fic gene family and Fap2 ⁺ fusobacteria in colorectal cancer microbiomes

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Fusobacterium is a bacterium associated with colorectal cancer (CRC) tumorigenesis, progression, and metastasis. Fap2 fusobacteria-specific outer membrane galactose-binding lectin that mediates adherence to invasion of CRC tumors. Advances in omics analyses provide an opportunity profile identify microbial genomic features correlate the cancer-associated bacterial virulence factor Fap2. Here, we analyze genomes colon tumor isolates find family post-translational modification enzymes containing Fic domains positivity these strains. We demonstrate genes expand presence fusobacterial pangenome. Through comparative analysis, Fap2+ Fusobacteriota are highly enriched gene families compared other human gut microbiome taxa. Using global data set shotgun metagenomes, show frequently co-occur fecal microbiomes individuals late-stage CRC. further characterize specific harbored by animalis detect recombination events elements horizontal transfer via synteny analysis loci. Exposure F. strain adenocarcinoma cell line increases expression virulence-associated adhesins. Finally, proteins synthesized as peptides detectable monoculture supernatants. Taken together, our study uncovers potential factors genomes.IMPORTANCEAccumulating support members intra-tumoral microbiota critically influence progression. Yet, relatively little known about non-adhesin may carcinogenesis. Our assays fusobacteria domain-containing genes, well-studied pathogenic bacteria, features. The encoded expressed merit future investigation assess their roles development

Language: Английский

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Role of Fungi in Tumorigenesis: Promises and Challenges

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2025, Volume and Issue: 20(1), P. 459 - 482

Published: Jan. 24, 2025

The mycobiome plays a key role in the host immune responses homeostasis and inflammation. Recent studies suggest that an imbalance gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, cancers. Pathogenic can colonize specific organs, gut has been linked development progression of various cancers, including colorectal, breast, head neck, pancreatic Some fungal species promote tumorigenesis by triggering complement system. However, immunocompromised patients, also inhibit this activation establish life-threatening infections. Interestingly, interaction bacteria induce unique responses. breakthroughs advancements high-throughput sequencing tumor mycobiomes are highlighting novel diagnostic therapeutic opportunities for cancer. We discuss latest developments field cancer potential benefits challenges antifungal therapies.

Language: Английский

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Dietary Restrictions and Cancer Prevention: State of the Art

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 503 - 503

Published: Jan. 29, 2025

Worldwide, almost 10 million cancer deaths occurred in 2022, a number that is expected to rise 16.3 by 2040. Primary prevention has long been acknowledged as crucial approach reducing incidence. In fact, between 30 and 50 percent of all tumors are known be preventable eating healthy diet, staying active, avoiding alcohol, smoking, being overweight. Accordingly, many international organizations have created tumor guidelines, which underlie the importance following diet emphasizes plant-based foods while minimizing consumption red/processed meat, sugars, processed foods, alcohol. However, further research needed define relationship effect specific diets or nutritional components on prevention. Interestingly, reductions food intake dietetic restrictions can extend lifespan yeast, nematodes, flies, rodents. Despite controversial results humans, those approaches potential ameliorate health via direct indirect effects signaling pathways involved onset. Here, we describe latest knowledge cancer-preventive dietary biochemical processes involved. Molecular, preclinical, clinical studies evaluating different fasting strategies will also reviewed.

Language: Английский

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Inhibition of Atg7 in intestinal epithelial cells drives resistance against Citrobacter rodentium

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 19, 2025

Abstract Autophagy, a cytoprotective mechanism in intestinal epithelial cells, plays crucial role maintaining homeostasis. Beyond its cell-autonomous effects, the significance of autophagy these cells is increasingly acknowledged dynamic interplay between microbiota and immune response. In context colon cancer, epithelium disruption has been identified as critical factor influencing tumor development. This modulates composition gut microbiota, eliciting an anti-tumoral Here, we report that Atg7 deficiency shapes leading to associated limitation colitis induced by Citrobacter rodentium infection. Mice with inducible, epithelial-cell-specific deletion gene, Atg7, exhibited enhanced clearance C. , mitigated hyperplasia, reduced pathogen-induced goblet cell loss. protective effect linked higher proportion neutrophils phagocytic early phase At later stages, it downregulation pro-inflammatory pathways increase Th17 Treg responses—immune responses known for their roles against infection, modulated specific microbiota. Fecal transplantation antibiotic treatment approaches revealed Atg7-deficiency-shapped especially Gram-positive bacteria, playing central driving resistance summary, our findings highlight inhibiting contributes homeostasis preventing detrimental inflammation through microbiota-mediated colonization . underscores played shaping promoting immune-mediated enteropathogens.

Language: Английский

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