Molecular & Cellular Toxicology最新文献

Background

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, causing significant impairment in daily life. It typically results from the compromised skin barriers and induces the Th2-dominant immune responses, which is heavily influenced by Interleukin-33 (IL-33). Meanwhile, snake venom has been known to be effective for various medical treatments. But, its role and mechanism in AD treatment are yet to be explored.

Objective

This study aimed to explore the therapeutic potential of cobrotoxin (CoTX), a single peptide from snake venom, in treating allergic AD via in vitro and in vivo models.

Results

Purified CoTX inhibited degranulation in RBL-2H3 cells, a marker for allergic inflammation. It reduced IgE secretion from B cells and modulated IL-33 expression in keratinocytes. CoTX effectively regulated both allergic and pseudoallergic pathways, suggesting its suppressive control over early and late stages of allergic reactions. The study also investigated CoTX’s impact on the IL-33 receptor ST2 and associated signaling proteins. The result was that CoTX inhibited IL-33- and IgE-induced activation, phosphorylation of MK2, and transactivation of NF-κB. In a DNCB-induced AD mouse model, CoTX treatment significantly improved AD symptoms and reduced epidermal thickness and mast cell infiltration. Finally, CoTX lowered serum IgE and IL-4 levels.

Conclusion

The study suggests that CoTX has anti-allergic and anti-inflammatory effects in allergic AD. By targeting IL-33 and IgE pathways, CoTX demonstrated potential in regulating mast cell activation and inflammatory cytokine production. The observed improvements in the AD mouse model indicate CoTX as a promising candidate for further research towards developing effective and safe treatments for AD.

Background

Oral cancer is a very familiar tumor together with a gravely effect on the life of human. GPD1 has been verified to join into the regulation of multifold cancers’ progression through being a suppressor. Interestingly, it has been revealed that GPD1 overexpression activated the PI3K/AKT signaling pathway. However, the regulatory functions of GPD1 on the PI3K/AKT/GSK-3β pathway in oral cancer progression keep vague, and need more investigations.

Objectives

To investigate the regulation function and mechanism of GPD1 in oral cancer.

Results

It was demonstrated that GPD1 exhibited lower expression in oral cancer. Moreover, overexpression of GPD1 relieved cell proliferation and strengthened cell apoptosis in oral cancer. Overexpression of GPD1 weakened cell migration and invasion in oral cancer. In addition, it was confirmed that overexpression of GPD1 suppressed mitochondrial function in oral cancer. At last, it was illustrated that GPD1 triggered the PI3K/AKT/GSK-3β pathway.

Conclusion

For the first time, this work manifested that GPD1 inhibited the proliferation, migration and invasion of oral cancer cells by inhibiting mitochondrial function through triggering the PI3K/AKT/GSK-3β pathway. This discovery hinted that GPD1 may be a serviceable biomarker for the treatment of oral cancer.

Background

Neurodegenerative diseases show various phenotypes of molecular and cellular malfunction including mitochondrial dysfunction and neuroinflammation. These molecular dynamics are based on the epigenetic regulation of the gene expression in the cells, which are vulnerable to progressive neurodegeneration. Histone deacetylases (HDAC) are the enzymes that remove acetyl group from histones or non-histone proteins for the transcriptional control. Thus, HDAC inhibitors (HDACi) have been proposed as prominent drugs for neurodegenerative diseases.

Objectives

In this study, we explain the molecular targets of the HDACi in the processes of neurodegeneration and neuroprotection.

Results

Treatment with HDACi altered the expression of specific genes that are associated with mitochondrial bioenergetics and neuroinflammation.

Conclusions

Mitochondrial bioenergetics- and neuroinflammation-related molecular targets of HDACi may be the key to the use of HDACi therapy for neurodegenerative diseases.

Purpose of review

We aimed to discover molecular targets of HDACi in progressive neurodegeneration and to use these targets in potential therapeutics to induce neuroprotection.

Recent findings

HDACi reverse cellular pathology in a mechanism involving mitochondrial bioenergetics and neuroinflammation, and the result is alleviation of pathologic phenotypes of neurodegenerative diseases.

Background

Dementia is a progressive neurological disorder which is clinically characterized by memory loss, behavioral symptoms, and loss of ability to live a normal life. Dementia patients may have to cope with permanent and irreversible symptoms.

Purpose of Review

Although a new drug for dementia with beta-amyloid-removal function has recently received FDA approval, the effect of delaying the progression of dementia is still insignificant, but the cost is expensive. On the other hand, studies on the effects of exercise in dementia have implied that the incidence of dementia or cognitive decline could be efficiently controlled by exercise.

Recent Findings

The cognitive neuroprotective effect of exercise was supported by cross-sectional studies in which physically fit seniors showed larger hippocampal or gray matter volumes than unfit seniors. In addition, multiple animal studies demonstrate that exercise promotes neuroplasticity through induction of neurotropic factors, with improved outcomes on cognitive functions.

Conclusion

In this review, we discuss the effects of conventional mode of physical exercise, cognitive (neuromuscular) exercise, and combined exercise in the prevention of dementia, and highlight the prospects for new exercise programs using digital technology that are being recently developed to reduce cognitive decline. Exercise should be importantly considered as a non-pharmacological therapeutic strategy for cognitive decline and dementia.

Introduction

Non-small cell lung cancer (NSCLC) is a heterogeneous series of tumors. Given the implication of microRNA-29b-3p (miR-29b-3p) in cisplatin resistance in NSCLC, this study expounded on the further mechanism.

Methods

A549 cells and cisplatin-resistant cells A549/DDP were selected. A549/DDP cells were manipulated with miR-29b-3p mimics/MCL-1 siRNA. miR-29b-3p and MCL levels were assessed. Cell sensitivity to cisplatin of different concentrations was examined by CCK-8. A549/DDP cell apoptosis under 10 µM cisplatin treatment was tested by flow cytometry. The targeted relationship between miR-29b-3p and MCL-1 was analyzed by TargetScan database and dual-luciferase assay. miR-29b-3p and MCL-1 were overexpressed to study whether miR-29b-3p regulated A549/DDP cell drug resistance by targeting MCL-1. To verify the effect of miR-29b-3p on DDP sensitivity in vivo, nude mice were subcutaneously injected with A549/DDP cells carrying the miR-29b-3p overexpressing lentiviral vector or the corresponding control vector to establish the nude mouse xenograft tumor model, and after 3 weeks, injected with DDP via tail vein for 2 weeks.

Results

miR-29b-3p level in A549/DDP cells was diminished and MCL-1 expression was raised. miR-29b-3p overexpression or MCL-1 silencing enhanced A549/DDP cell sensitivity to cisplatin by promoting apoptosis. miR-29b-3p targeted MCL-1. MCL-1 overexpression partially averted miR-29b-3p overexpression-promoted cisplatin sensitivity and apoptosis. Tumor volume/weight/MCL-1 level in the A549/DDP/miR mimics + DDP group were reduced, and miR-29b-3p was up-regulated versus the A549/DDP/mimics NC + DDP group. Overexpression of miR-29b-3p induced apoptosis in tumor tissues of NSCLC mice.

Conclusion

miR-29b-3p targeted MCL-1, thus promoting apoptosis and enhancing A549/DDP cell sensitivity to cisplatin.

Background

Periodontitis is a multi-microbial infection characterized by a destructive inflammatory process that affects periodontal tissues. The extracts of traditional Chinese medicine have been reported to be involved in the regulation of the treatment of periodontitis. Licochalcone B (LicB) has been shown to have a wide range of pharmacological activities in diversiform diseases. However, the regulatory functions of LicB and its related mechanisms have not been explored in periodontitis.

Objective

In this study, our work focused on investigating the regulatory functions of LicB in LPS-stimulated PDLCs.

Results

Periodontal ligament cells (PDLCs) were first treated with LPS (10 μg/mL) to simulate periodontitis cell model. The results showed that cell proliferation was decreased after LPS treatment, but this effect was restored after LicB treatment. In addition, LicB inhibited inflammatory response and oxidative stress in LPS-induced PDLCs. Furthermore, the osteogenic differentiation was inhibited after LPS treatment, but this change was reversed by LicB treatment. Lastly, it was demonstrated that LicB blocked the NF-κB/NLRP3 signaling pathway.

Conclusion

This study for the first time demonstrated that LicB inhibited the inflammatory response and oxidative stress of PDLCs in periodontitis, suggesting that LicB may be a useful drug for periodontitis treatment.

Background

Tolylfluanid is a phenylsulfamide fungicide used to mitigate enormous losses in agriculture and coastal industries. Previous studies have reported that exposure to tolylfluanid causes metabolic dysfunction, such as fat accumulation. Additionally, exposure to tolylfluanid used to be detected in strawberries at levels exceeding the maximum residue limit. However, no studies on early developmental toxicity in zebrafish models have been reported.

Objectives

This study aimed to investigate the toxic effects of tolylfluanid on the early stages of zebrafish development.

Results

At low tolylfluanid concentrations, survival rates, hatching rates, and yolk sac morphology remained unchanged. However, body length and eye size were slightly reduced compared to those of the control. In particular, olig2 transgenic zebrafish exposed to tolylfluanid exhibited impaired motor neuron formation, leading to reduced motor neuron length. Furthermore, tolylfluanid decreased liver size in fabp10a transgenic zebrafish larvae, inducing liver-specific red fluorescence. However, tolylfluanid exposure did not affect the vasculature of zebrafish embryos in the fli1a:eGFP transgenic model.

Conclusion

Tolylfluanid disrupts organogenesis, particularly in motor neurons and the liver, during early development in zebrafish. Additionally, the results provide reference points for the concentration conditions that can be used in aquatic ecosystems.

Background

Hepatic steatosis is characterized by lipid accumulation in hepatocytes. Cheong-sang-gyeon-tong-tang is a major prescription for all types of headaches in traditional East Asian medicine.

Objective

This study aimed to investigate the pharmacological effects of Cheong-sang-gyeon-tong-tang extract (CG) on high-fat diet (HFD)-induced hepatic steatosis in mice and to explore the underlying mechanism.

Results

Treatment with CG significantly reduced body weight, liver weight, and epididymal fat mass, as well as improved the serum and hepatic lipid profiles in the HFD-induced fatty liver mouse model. Further, CG alleviated lipid accumulation in HFD-fed mice by controlling lipid metabolism, including triglyceride and cholesterol synthesis, and fatty acid oxidation at the mRNA level. CG also regulated the expression of cholesterol regulatory proteins in HFD-induced fatty liver mice.

Conclusions

These results indicate that CG alleviates hepatic steatosis by regulating cholesterol homeostasis in HFD-induced fatty liver mice, thus improving our understanding of the mechanisms by which CG improves hepatic steatosis. Therefore, we propose CG as a therapeutic candidate for lipid metabolic disorders such as fatty liver disease.

Abstract