Cellular senescence precipitates a decline in physiological activities and metabolic functions, often accompanied by heightened inflammatory responses, diminished immune function, and impaired tissue and organ performance. Despite extensive research, the mechanisms underpinning cellular senescence remain incompletely elucidated. Emerging evidence implicates circadian rhythm and hypoxia as pivotal factors in cellular senescence. Circadian proteins are central to the molecular mechanism governing circadian rhythm, which regulates homeostasis throughout the body. These proteins mediate responses to hypoxic stress and influence the progression of cellular senescence, with protein Brain and muscle arnt-like 1 (BMAL1 or Arntl) playing a prominent role. Hypoxia-inducible factor-1α (HIF-1α), a key regulator of oxygen homeostasis within the cellular microenvironment, orchestrates the transcription of genes involved in various physiological processes. HIF-1α not only impacts normal circadian rhythm functions but also can induce or inhibit cellular senescence. Notably, HIF-1α may aberrantly interact with BMAL1, forming the HIF-1α-BMAL1 heterodimer, which can instigate multiple physiological dysfunctions. This heterodimer is hypothesized to modulate cellular senescence by affecting the molecular mechanism of circadian rhythm and hypoxia signaling pathways. In this review, we elucidate the intricate relationships among circadian rhythm, hypoxia, and cellular senescence. We synthesize diverse evidence to discuss their underlying mechanisms and identify novel therapeutic targets to address cellular senescence. Additionally, we discuss current challenges and suggest potential directions for future research. This work aims to deepen our understanding of the interplay between circadian rhythm, hypoxia, and cellular senescence, ultimately facilitating the development of therapeutic strategies for aging and related diseases.

• Klíčová slova
• Cellular senescence, Circadian rhythm, Hypoxia, Potential therapy, Relationships,
• MeSH
• cílená molekulární terapie MeSH
• cirkadiánní rytmus * fyziologie   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• hypoxie buňky MeSH
• hypoxie metabolismus   patofyziologie   MeSH
• lidé MeSH
• signální transdukce MeSH
• stárnutí buněk * MeSH
• transkripční faktory ARNTL metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• transkripční faktory ARNTL MeSH

The complex interaction between circadian rhythms and physiological functions is essential for maintaining human health. At the heart of this interaction lies the PERIOD proteins (PERs), pivotal to the circadian clock, influencing the timing of physiological and behavioral processes and impacting oxidative stress, immune functionality, and tumorigenesis. PER1 orchestrates the cooperation of the enzyme GPX1, modulating mitochondrial dynamics in sync with daily rhythms and oxidative stress, thus regulating the mechanisms managing energy substrates. PERs in innate immune cells modulate the temporal patterns of NF-κB and TNF-α activities, as well as the response to LPS-induced toxic shock, initiating inflammatory responses that escalate into chronic inflammatory conditions. Crucially, PERs modulate cancer cell behaviors including proliferation, apoptosis, and migration by influencing the levels of cell cycle proteins and stimulating the expression of oncogenes c-Myc and MDM2. PER2/3, as antagonists in cancer stem cell biology, play important roles in differentiating cancer stem cells and in maintaining their stemness. Importantly, the expression of Pers serve as a significant factor for early cancer diagnosis and prognosis. This review delves into the link between circadian rhythm regulator PERs, disruptions in circadian rhythm, and oncogenesis. We examine the evidence that highlights how dysfunctions in PERs activities initiate cancer development, aid tumor growth, and modify cancer cell metabolism through pathways involved in oxidative stress and immune system. Comprehending these connections opens new pathways for the development of circadian rhythm-based therapeutic strategies, with the aims of boosting immune responses and enhancing cancer treatments.

• Klíčová slova
• Cancer, Circadian rhythms, Immune response, Oxidative stress, PERs,
• MeSH
• cirkadiánní proteiny Period metabolismus   genetika   MeSH
• cirkadiánní rytmus * fyziologie   MeSH
• imunita MeSH
• karcinogeneze MeSH
• lidé MeSH
• nádory * imunologie   metabolismus   patologie   MeSH
• oxidační stres * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cirkadiánní proteiny Period MeSH

BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.

• Klíčová slova
• Neurodegenerative diseases, blood-brain barrier, dietary adaptations., gut microbiota, microbiota-gut-brain axis, therapy,
• Publikační typ
• časopisecké články MeSH

Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity. In the realm of innate immunity, aging brings about changes in the number and function of various immune cells, including neutrophils, monocytes, and macrophages. Additionally, certain immune pathways, like the cGAS-STING, become activated. These alterations can potentially result in telomere damage, the disruption of cytokine signaling, and impaired recognition of pathogens. The adaptive immune system, too, undergoes a myriad of changes as age advances. These include shifts in the number, frequency, subtype, and function of T cells and B cells. Furthermore, the human gut microbiota undergoes dynamic changes as a part of the aging process. Notably, the interplay between immune changes and gut microbiota highlights the gut's role in modulating immune responses and maintaining immune homeostasis. The gut microbiota of centenarians exhibits characteristics akin to those found in young individuals, setting it apart from the microbiota observed in typical elderly individuals. This review delves into the current understanding of how aging impacts the immune system and suggests potential strategies for reversing aging through interventions in immune factors.

• Klíčová slova
• adaptive immunity, aging, cGAS-STING, gut microbiota, gut microbiota aging, innate immunity,
• MeSH
• adaptivní imunita * MeSH
• lidé MeSH
• přirozená imunita * MeSH
• stárnutí * imunologie   MeSH
• střevní mikroflóra * imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Aging encompasses a wide array of detrimental effects that compromise physiological functions, elevate the risk of chronic diseases, and impair cognitive abilities. However, the precise underlying mechanisms, particularly the involvement of specific molecular regulatory proteins in the aging process, remain insufficiently understood. Emerging evidence indicates that c-Jun N-terminal kinase (JNK) serves as a potential regulator within the intricate molecular clock governing aging-related processes. JNK demonstrates the ability to diminish telomerase reverse transcriptase activity, elevate β-galactosidase activity, and induce telomere shortening, thereby contributing to immune system aging. Moreover, the circadian rhythm protein is implicated in JNK-mediated aging. Through this comprehensive review, we meticulously elucidate the intricate regulatory mechanisms orchestrated by JNK signaling in aging processes, offering unprecedented molecular insights with significant implications and highlighting potential therapeutic targets. We also explore the translational impact of targeting JNK signaling for interventions aimed at extending healthspan and promoting longevity.

• Klíčová slova
• JNK, aging, longevity, molecular insights, therapeutic targets,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Biodiversity conservation amidst the uncertainty of climate change presents unique challenges that necessitate precise management strategies. The study reported here was aimed at refining understanding of these challenges and to propose specific, actionable management strategies. Employing a quantitative literature analysis, we meticulously examined 1268 research articles from the Web of Science database between 2005 and 2023. Through Cite Spaces and VOS viewer software, we conducted a bibliometric analysis and thematic synthesis to pinpoint emerging trends, key themes, and the geographical distribution of research efforts. Our methodology involved identifying patterns within the data, such as frequency of keywords, co-authorship networks, and citation analysis, to discern the primary focus areas within the field. This approach allowed us to distinguish between research concentration areas, specifically highlighting a predominant interest in Environmental Sciences Ecology (67.59 %) and Biodiversity Conservation (22.63 %). The identification of adaptive management practices and ecosystem services maintenance are central themes in the research from 2005 to 2023. Moreover, challenges such as understanding phenological shifts, invasive species dynamics, and anthropogenic pressures critically impact biodiversity conservation efforts. Our findings underscore the urgent need for precise, data-driven decision-making processes in the face of these challenges. Addressing the gaps identified, our study proposes targeted solutions, including the establishment of germplasm banks for at-risk species, the development of advanced genomic and microclimate models, and scenario analysis to predict and mitigate future conservation challenges. These strategies are aimed at enhancing the resilience of biodiversity against the backdrop of climate change through integrated, evidence-based approaches. By leveraging the compiled and analyzed data, this study offers a foundational framework for future research and practical action in biodiversity conservation strategies, demonstrating a path forward through detailed analysis and specified solutions.

• Klíčová slova
• Biodiversity, Climate change, Conservation, Ecosystem service, Management,
• MeSH
• biodiverzita * MeSH
• ekosystém MeSH
• klimatické změny * MeSH
• zachování přírodních zdrojů * metody   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Deoxynivalenol (DON), a potent mycotoxin, exhibits strong immunotoxicity and poses a significant threat to human and animal health. Cell senescence has been implicated in the immunomodulatory effects of DON; however, the potential of DON to induce cell senescence remains inadequately explored. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) serves as a crucial target of mycotoxins and is closely involved in cell senescence. To investigate this potential, we employed the RAW264.7 macrophage model and treated the cells with varying concentrations of DON (2-8 μM) for 24 h. Transcriptome analysis revealed that 2365 genes were significantly upregulation while 2405 genes were significantly decreased after exposure to DON. KEGG pathway enrichment analysis demonstrated substantial enrichment in pathways associated with cellular senescence and hypoxia. Remarkably, we observed a rapid and sustained increase in HIF-1α expression following DON treatment. DON induced cell senescence through the activation of the p53/p21WAF1/CIP1 (p21) and p16INK4A (p16) pathways, while also upregulating the expression of nuclear factor-κB, leading to the secretion of senescence-associated secretory phenotype (SASP) factors, including IL-6, IL-8, and CCL2. Crucially, HIF-1α positively regulated the expression of p53, p21, and p16, as well as the secretion of SASP factors. Additionally, DON induced cell cycle arrest at the S phase, enhanced the activity of the senescence biomarker senescence-associated β-galactosidase, and disrupted cell morphology, characterized by mitochondrial damage. Our study elucidates that DON induces cell senescence in RAW264.7 macrophages by modulating the HIF-1α/p53/p21 pathway. These findings provide valuable insights for the accurate prevention of DON-induced immunotoxicity and associated diseases.

• Klíčová slova
• Cell senescence, DON, HIF-1α, Hypoxia, Immune toxicity,
• MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus   genetika   MeSH
• inhibitor p21 cyklin-dependentní kinasy * metabolismus   genetika   MeSH
• makrofágy * účinky léků   metabolismus   MeSH
• myši MeSH
• nádorový supresorový protein p53 * metabolismus   MeSH
• RAW 264.7 buňky MeSH
• signální transdukce * účinky léků   MeSH
• stárnutí buněk * účinky léků   MeSH
• trichotheceny * toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Cdkn1a protein, mouse MeSH Prohlížeč
• deoxynivalenol MeSH Prohlížeč
• faktor 1 indukovatelný hypoxií - podjednotka alfa * MeSH
• Hif1a protein, mouse MeSH Prohlížeč
• inhibitor p21 cyklin-dependentní kinasy * MeSH
• nádorový supresorový protein p53 * MeSH
• trichotheceny * MeSH
• Trp53 protein, mouse MeSH Prohlížeč

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated β-galactosidase activity in in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of β-amyloid and tau-protein tangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase and nuclear factor kappa B signaling attenuate β-amyloid load and prevent tau-protein tangle deposition, thereby improving cognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associated with increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α, and IL-1β secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerable neuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggesting strategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.

• Klíčová slova
• Alzheimer’s disease, Amyloid β · tau protein, Cellular senescence, Neurodegenerative diseases, Telomere shortening,
• MeSH
• Alzheimerova nemoc MeSH
• amyloidní beta-protein metabolismus   MeSH
• lidé MeSH
• neurodegenerativní nemoci * MeSH
• Parkinsonova nemoc metabolismus   MeSH
• sekreční fenotyp asociovaný se senescencí MeSH
• signální transdukce MeSH
• stárnutí buněk * účinky léků   MeSH
• zkracování telomer účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• amyloidní beta-protein MeSH

The special issue "New Insight into Mycotoxins and Bacterial Toxins: Toxicity Assessment, Molecular Mechanism and Food Safety" in Food and Chemical Toxicology contains 19 articles on current hot topics in mycotoxins and bacterial toxins. Dietary exposure to mycotoxins and risk assessments are reported in this issue. Molecular mechanisms of multiple mycotoxins and emerging mechanisms of toxicity are especially concerned by researchers. Moreover, mycotoxin-detoxifying substances and antimicrobial agents are also fully investigated in the context. This special issue will help to further understand the mycotoxins and bacterial toxins, casting new light for the control of food safety.

• Klíčová slova
• Bacterial toxins, Food safety, Molecular mechanism, Mycotoxin-detoxifying, Mycotoxins,
• MeSH
• bakteriální toxiny * toxicita   MeSH
• bezpečnost potravin * MeSH
• hodnocení rizik MeSH
• kontaminace potravin analýza   MeSH
• lidé MeSH
• mykotoxiny * toxicita   analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• úvodní články MeSH
• úvodníky MeSH
• Názvy látek
• bakteriální toxiny * MeSH
• mykotoxiny * MeSH

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils.

• Klíčová slova
• Antitumor activity, Cancer, Immunotherapy, Neutrophils, Protumor activity,
• MeSH
• imunoterapie * metody   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory * imunologie   terapie   metabolismus   patologie   MeSH
• neutrofily * imunologie   metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH