Cell Biochemistry and Function最新文献

Preclinical animal research plays a crucial role in studying colorectal cancer (CRC). Mouse models allow for testing the efficacy of potential medications and understanding the mechanisms behind CRC development. Carcinogens like 1,2-Dimethylhydrazine (DMH) and Azoxymethane (AOM) are used to induce CRC in these models, enabling researchers to investigate various treatment approaches. The availability of diverse animal strains facilitates the study of CRC progression and metastasis. By examining literature on animal models, researchers can assess the accuracy of reproducing different stages of CRC, from crypts to polyps and tumors. Animal models are essential for studying the tumor microenvironment and its impact on CRC. These models replicate key features of human CRC, including angiogenesis and immune responses. Both immunocompetent and immunocompromised rodents are used to evaluate immunotherapeutic drugs. This review summarizes common murine models for CRC and their applications in translational research. Future trends in this field likely include further advancements in animal models for studying tumor biology.

ZIP14 is a member of the SLC39A (ZIP) family of metal transporters, primarily facilitating the cellular influx of divalent metals including manganese (Mn), zinc (Zn), and iron (Fe). Previous studies have demonstrated that Zip14 knockout (Zip14^-/-) mice exhibit significant increases in whole blood and brain Mn levels. However, the impact of ZIP14 deletion on metal homeostasis within the cerebrospinal fluid (CSF) remained unexplored. In this study, we comprehensively assessed Mn, Zn, Fe, sodium (Na), potassium (K), and calcium (Ca) levels in whole blood, serum, and CSF of male and female Zip14^-/- mice to elucidate both systemic and central nervous system (CNS)-specific alterations in metal homeostasis. Our findings reveal that Zip14^-/- mice exhibit pronounced Mn accumulation, with CSF Mn levels increasing by approximately 15-fold in males and 46-fold in females compared to wild-type controls. Correspondingly, blood Mn levels rose 23-fold in males and 17-fold in females, while serum Mn levels increased 10-fold and 15-fold, respectively. In contrast, Zn and Fe levels in whole blood and serum remained comparable between Zip14^-/- and wild-type mice. However, significant elevations in CSF Zn were observed, with a sevenfold increase in males and a 16-fold increase in females, alongside a threefold rise in CSF Fe levels in females. The CSF to serum ratios of Zn and Fe remained below 1 but were increased in the knockout mice, suggesting the activation of alternative metal transporters in the absence of ZIP14, which may contribute to the increased Mn accumulation in the CSF as well. Importantly, Na⁺ and K⁺ levels in whole blood, serum, and CSF were unaltered in Zip14^-/- mice, indicating that ZIP14 deletion does not broadly disrupt systemic electrolyte balance or compromise blood—CSF barrier integrity. Conversely, CSF Ca²⁺ levels were significantly reduced by 33% in male and 23% in female Zip14^-/- mice, suggesting a specific effect of ZIP14 on calcium homeostasis within the CNS.

Colorectal cancer ranks among the most common malignancies worldwide. Our previous study indicated Carbonic anhydrase 8 (CA8) is linked to cell proliferation and mobility in colon cancer cells. In the present study, we observed a significant increase in the expression of mutant p53 R273H/P309S in colon cancer cell lines (SW480 and SW620) with stably downregulated CA8. P53, a well-known tumor suppressor gene, is frequently mutated in cancer cells, leading to poor prognosis and drug resistance. Although p53 acts as a transcription factor, the increased mutant p53 did not activate downstream target molecules, suggesting activation defects of mutant p53 R273H/P309S. Furthermore, transient downregulation of CA8 did not alter p53 expression, indicating that the observed increase in mutant p53 in stable cells may be a compensatory effect for cell survival. Given that p53 shares similar consensus sequences at GC-boxes with specific protein 1 (Sp1), a predominant transcription factor for CA8 regulation, we examined the relationship between CA8, p53 and Sp1 in HCT116 and SW620 cells harboring wild-type (WT) or mutant p53, respectively. Notably, transient downregulation of p53 or Sp1 led to a significant decrease in CA8 at both mRNA and protein levels in HCT116 and SW620 cells. Additionally, immunoprecipitation results revealed a protein-protein interaction between Sp1 and p53, suggesting that their interaction may be involved in the regulation of CA8 expression. Although the precise mechanism by which Sp1 and p53 regulate CA8 expression remains unclear, we are the first to report that both Sp1 and p53 are involved in the regulation of the novel hCA8 gene. By further unraveling the interplay among CA8, p53, and Sp1, we hope to pave the way for new therapeutic approaches in colon cancer treatment.

The role of IL-10-producing regulatory B cells in inflammatory diseases has recently gained substantial attention. Here, we evaluated the function of mouse bone marrow mesenchymal stem cell-derived exosomes (BMMSC-Exos) and their effect on B-cell differentiation. This study aimed to establish an association between BMMSC-Exos and purified B cells and further explored the anti-inflammatory effect of B10 cells. The expression of inflammatory factors, such as IL-1β, TNF-α, and bone metabolism-related factors, including RANKL, OPG, and secreted IL-10, was investigated by RT-qPCR and ELISA. Populations of CD1d^highCD5⁺ B cells were analyzed by flow cytometry and immunofluorescence. Cell viability was assessed by CCK8 assay. The results showed that when B cells were separated from BMMSCs by Transwell, IL-1β, TNF-α, and RANKL were downregulated, whereas IL-10, OPG/RANKL, and CD1d^highCD5⁺ Breg proportion were upregulated in the cocultured groups. Conversely, when B cells were cultured with BMMSC-Exos, increasing concentrations of exosomes increased the proportion of CD1d^highCD5⁺ and IL-10⁺CD45⁺ Bregs; however, the secretion of both pro-inflammatory cytokines and IL-10 were decreased. We found that BMMSC-Exos induce the differentiation of B cells toward the CD1d^highCD5⁺ and IL-10⁺CD45⁺ Breg phenotype but cannot increase the secretion of IL-10 in vitro.

Cervical cancer remains a significant global health burden, with its etiology intricately linked to hormonal influences such as estrogen and progesterone. The effect of estrogen on cervical cancer is dependent upon factors like estrogen receptor subtype and microenvironmental context. Conversely, progesterone has a more complex role, acting as an inducer as well as inhibitor, by coordinating with tumor suppressor genes and cell proliferation markers. Understanding the interplay among these hormones, HPV infection, and cervical carcinogenesis is crucial for improving current preventive strategies and therapeutic interventions. This review outlines the latest insights on how hormones influence cervical cancer development, highlighting their protective and inhibitory effects. It explores the interaction between HPV oncogenes and hormones in cervical cancer progression. Additionally, it consolidates existing knowledge and identifies future research directions, underscoring the potential of hormone modulation as a therapeutic strategy for cervical cancer.

The metabolic properties of disulfidoptosis targeting cancer cells have become a new key to unlocking cancer treatment's lock. Conventional cancer therapies aim to kill tumor cells through apoptosis, but cell death is carried out by a network of cascading enzymes. Malignant cells can evade the death process by downregulating key enzymes or inhibiting death-inducing triggers, leading to cancer persistence and recurrence of cancer cells that are resistant to conventional therapies and immune escape, which has compelled researchers to explore new therapeutic avenues. Disulfidoptosis is triggered by the accumulation of excessive intracellular disulfides in cells with high expression of solute carrier family 7 member 11 (SLC7A11) under glucose starvation conditions, which simultaneously induces the breakage of intracellular disulfide bonds and leads to protein malfunction, thereby triggering cancer cell death. However, there is no comprehensive account of disulfidoptosis application in cancer therapy. This review comprehensively summarizes the mechanism of disulfidoptosis for cancer treatment, which provides new ideas for cancer treatment.

Kidney diseases, characterized by renal dysfunction, are the leading causes of death worldwide. It is crucial to prevent and treat kidney diseases to reduce their associated morbidity and mortality. Moderate physical exercise has been recognized to be advantageous for kidney health. Irisin is an exercise-induced myokine that was identified in 2012. It plays an important role in energy and bone metabolism, oxidative stress reduction, anti-inflammatory processes, cell death inhibition, and cardiovascular protection. However, the relationship between irisin and kidney diseases have not been fully elucidated. This review explores the role of irisin as a biomarker for kidney disease diagnosis and its associated complications, as well as the mechanisms through which it participates in various cell death pathways, such as apoptosis, autophagy, pyroptosis, and ferroptosis. Furthermore, irisin secretion levels were discussed to provide a basis for kidney disease prevention and treatment avenues, as well as therapeutic guidance for developing new and promising intervention strategies.

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