Pengyu Lei’s research while affiliated with Wenzhou University and other places

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Publications (19)


Micro/nano plastics in the urinary system: Pathways, mechanisms, and health risks
  • Literature Review

November 2024

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12 Reads

Environment International

Hang Huang

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Pengyu Lei

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Haiyang Yu

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[...]

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Lijun Wan

Phenethyl isothiocyanate inhibits the carcinogenic properties of hepatocellular carcinoma Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways

June 2024

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3 Reads

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1 Citation

Background Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatment options. Phenethyl isothiocyanate (PEITC) is a bioactive substance present primarily in the cruciferous vegetables. PEITC has exhibited anti-cancer properties in various cancers, including lung, bile duct, and prostate cancers. It has been demonstrated that PEITC can inhibit the proliferation, invasion, and metastasis of SK-Hep1 cells, while effectively inducing apoptosis and cell cycle arrest in HepG2 cells. However, knowledge of its anti-carcinogenic effects on Huh7.5.1 cells and its underlying mechanism remains elusive. In the present study, we aim to evaluate the anti-carcinogenic effects of PEITC on human HCC Huh7.5.1 cells. Methods MTT assay and colony formation assay was performed to investigate the anti-proliferative effects of PEITC against Huh7.5.1 cells. The pro-apoptosis effects of PEITC were determined by Annexin V-FITC/PI double staining assay by flow cytometry (FCM), mitochondrial transmembrane potential (MMP) measurement, and Caspase-3 activity detection. A DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was conducted to estimate the DNA damage in Huh7.5.1 cells induced by PEITC. Cell cycle progression was determined by FCM. Transwell invasion assay and wound healing migration assay were performed to investigate the impact of PEITC on the migration and invasion of Huh7.5.1 cells. In addition, transcriptome sequencing and gene set enrichment analysis (GSEA) were used to explore the potential molecular mechanisms of the inhibitory effects of PEITC on HCC. Quantitative real-time PCR (qRT-PCR) analysis was performed to verify the transcriptome data. Results MTT assay showed that treatment of Huh7.5.1 cells with PEITC resulted in a dose-dependent decrease in viability, and colony formation assay further confirmed its anti-proliferative effect. Furthermore, we found that PEITC could induce mitochondrial-related apoptotic responses, including a decrease of mitochondrial transmembrane potential, activation of Caspase-3 activity, and generation of intracellular reactive oxygen species. It was also observed that PEITC caused DNA damage and cell cycle arrest in the S-phase in Huh7.5.1 cells. In addition, the inhibitory effect of PEITC on the migration and invasion ability of Huh7.5.1 cells was assessed. Transcriptome sequencing analysis further suggested that PEITC could activate the typical MAPK, PI3K-Akt, and p53 signaling pathways, revealing the potential mechanism of PEITC in inhibiting the carcinogenic properties of Huh7.5.1 cells. Conclusion PEITC exhibits anti-carcinogenic activities against human HCC Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways. Our results suggest that PEITC may be useful for the anti-HCC treatment.


Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms

March 2024

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9 Reads

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1 Citation

Heliyon

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1β and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.


Figure 3. Reproductive effects of MNPs or MNPs and other pollutants on zebrafish. (a,b,c) Morphological changes in reproductive organs [100,101]; (a) copyright © 2022 Elsevier; (b,c) copyright © 2023 published by Elsevier; (f-h) changes in hormone levels [101,102]; (f) copyright © 2020 Elsevier; (g,h) copyright © 2023 Elsevier; (d,e,i) reproductive hormone gene expression [101-103]; (d) copyright © 2022 Elsevier; (e) copyright © 2020 Elsevier; (i) copyright © 2023 Elsevier. Spermatogenic cycle include spermatogonia (Sg), spermatocytes (Sc), spermatids (St), and spermatozoa (Sz). perinuclear oocytes (PO), cortical alveolar oocytes (CO), early vitellogenin oocytes (EV) and late vitellogenin oocytes (LV). Om is the ovum, Soc is the secondary oocyte, and Poc is the primary oocyte. The pentagram represents the vacuolated oocyte, and the red arrow represents the oocyte's missing linkage with the follicular cell layer. * p < 0.05, ** p < 0.01; the different letters represent the significance level (p < 0.05).
The effect of MNPs and their combination exposure with other contaminants on the reproductive system of zebrafish.
Cont.
Behavioral Studies of Zebrafish Reveal a New Perspective on the Reproductive Toxicity of Micro- and Nanoplastics
  • Literature Review
  • Full-text available

February 2024

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98 Reads

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6 Citations

Toxics

The escalating prevalence of microplastics and nanoplastics in aquatic environments is a major challenge affecting the behavior and reproductive health of aquatic organisms while posing potential risks to human health and ecosystems. This review focuses on the neurobehavioral changes and reproductive toxicity of MNPs in zebrafish and their relationships. At the same time, the neurobehavioral changes caused by MNPs were studied, and the synergistic effects of the interaction of these pollutants with other environmental contaminants were explored. In addition, zebrafish, as a model organism, provide valuable insights into the subtle but important effects of MNPs on reproductive behavior, which is critical for understanding reproductive success, suggesting that behavioral changes can serve as an early biomarker of reproductive toxicity. In addition, based on classical endocrine disruptor models and behavioral research methods, the current status of the research on the reproductive toxicity of MNPs in zebrafish was reviewed, which further indicated that the behavioral parameters of zebrafish can be used as an effective and rapid tool to evaluate the reproductive toxicity of MNPs. However, behavioral methods for rapidly assessing the toxicity of MNPs are still an area of exploration. To address limitations and challenges in the current scope of research, this review outlines future research directions with the aim of improving our understanding of the environmental and health impacts of MNPs. This work aims to inform targeted environmental policies and advance public health strategies to address the growing challenge of MNPs pollution.

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Recent Advances in Living Algae Seeding Wound Dressing: Focusing on Diabetic Chronic Wound Healing

September 2023

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234 Reads

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12 Citations

Diabetic chronic wounds (DCWs) are a severe complication of diabetes, and current treatments present several deficiencies, including unsatisfactory efficacy and inability to continuously supply oxygen. This review highlights the recent advances in a novel therapeutic strategy that addresses these challenges: considerable biological powerful inclusions, oxygen or hydrogen and ROS production, DCW glucose consumption, chemotaxis at the wound site, highly editable, great biological safety, low cost, and readily available. Over the past decade, this strategy has shown encouraging results in improving the healing delay induced by hyperglycemia, forming a new concept of “living material” application based on living algae. This review discusses the unique advantages of algae as a treatment strategy, the applications and characteristics of different types of living algae in wound dressings, and the challenges and improvement strategies for this innovative approach.


Figure 2. Enterocerebral neural pathways of the intestine and brain. (A) Enteroendocrine cells contact sensory nerve fibers. (B) Enteroendocrine cells of the colon and small intestine synapse interact with vagal tubercle neurons. Copyright © 2018, American Association for the Advancement of Science Publishing Group. Replicated with permission from Ref. [19].
Figure 3. Gut microbiota accelerates the development of AD through the immune system. The decrease in anti-inflammatory and increase in pro-inflammatory bacteria in the intestinal flora of AD patients leads to an increase in harmful metabolites and a decrease in beneficial metabolites in the gut. These changes accelerate neuroinflammatory and systemic inflammatory responses in AD patients and reduce Aβ protein clearance and repair of nerve damage, accelerate Tau protein phosphorylation, and Aβ protein deposition, thus accelerating the development of AD. Copyright © 2018, Elsevier Publishing Group. Replicated with permission from Ref. [33].
Figure 5. Improvement effect of probiotics, prebiotics and FMT on patients with AD. Probiotics, prebiotics and FMT can regulate the composition of intestinal flora, improve intestinal permeability, and increase beneficial metabolites in patients with AD. And reduce neuroinflammation, reduce the deposition of ad-related pathological proteins and improve cognitive impairment in patients with AD through neural, immune, and small molecular delivery systems.
Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential

August 2023

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42 Reads

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12 Citations

Aging and Disease

An essential regulator of neurodegenerative conditions like Alzheimer's disease (AD) is the gut microbiota. Alterations in intestinal permeability brought on by gut microbiota dysregulation encourage neuroinflammation, central immune dysregulation, and peripheral immunological dysregulation in AD, as well as hasten aberrant protein aggregation and neuronal death in the brain. However, it is unclear how the gut microbiota transmits information to the brain and how it influences brain cognition and function. In this review, we summarized the multiple pathways involved in the gut microbiome in AD and provided detailed treatment strategies based on the gut microbiome. Based on these observations, this review also discusses the problems, challenges, and strategies to address current therapeutic strategies.


Cell membrane nanomaterials composed of phospholipids and glycoproteins for drug delivery in inflammatory bowel disease: A review

August 2023

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34 Reads

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9 Citations

International Journal of Biological Macromolecules

Inflammatory bowel disease (IBD) is a serious chronic intestinal disorder with an increasing global incidence. However, current treatment strategies, such as anti-inflammatory drugs and probiotics, have limitations in terms of safety, stability, and effectiveness. The emergence of targeted nanoparticles has revolutionized IBD treatment by enhancing the biological properties of drugs and promoting efficiency and safety. Unlike synthetic nanoparticles, cell membrane nanomaterials (CMNs) consist primarily of biological macromolecules, including phospholipids, proteins, and sugars. CMNs include red blood cell membranes, macrophage membranes, and leukocyte membranes, which possess abundant glycoprotein receptors and ligands on their surfaces, allowing for the formation of cell-to-cell connections with other biological macromolecules. Consequently, they exhibit superior cell affinity, evade immune responses, and target inflammation effectively, making them ideal material for targeted delivery of IBD therapies. This review explores various CMNs delivery systems for IBD treatment. However, due to the complexity and harsh nature of the intestinal microenvironment, the lack of flexibility or loss of selectivity poses challenges in designing single CMNs delivery strategies. Therefore, we propose a hierarchically programmed delivery modality that combines CMNs with pH, charge, ROS and ligand-modified responsive nanoparticles. This approach significantly improves delivery efficiency and points the way for future research in this area.


The potential of white-rot fungi for algal control: Mechanisms, Strategies, and Challenges

July 2023

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36 Reads

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7 Citations

Environmental Research

As human society and industrialization have progressed, harmful algal blooms have contributed to global ecological pollution which makes the development of a novel and effective algal control strategy imminent. This is because existing physical and chemical methods for dealing with the problem have issues like cost and secondary pollution. Benefiting from their environmentally friendly and biocompatible properties, white-rot fungi (WRF) have been studied to control algal growth. WRF control algae by using algae for carbon or nitrogen, antagonism, and enhancing allelopathies. It can be better applied to practice by immobilization. This paper reviews the mechanism for WRF control of algae growth and its practical application. It demonstrates the limitations of WRF controlling algae growth and aids the further study of biological methods to regulate eutrophic water in algae growth research. In addition, it provides theoretical support for the fungi controlling algae growth.


Escherichia coli Nissle 1917 ghosts alleviate inflammatory bowel disease in zebrafish

July 2023

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20 Reads

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9 Citations

Life Sciences

Escherichia coli Nissle 1917 (EcN) has become a research hotspot in inflammatory bowel disease (IBD). It has a strong targeting effect on the colon, and has some therapeutic effect on inflammatory bowel disease. EcN is prepared into EcN ghosts, which also retain EcN's biological characteristics. Consequently, EcN ghosts are used for drug delivery. This study evaluated the safety and efficacy of EcN ghosts as carriers of drugs for treating IBD in zebrafish. Caco-2 cell adhesion experiments and zebrafish intestinal adhesion experiments demonstrated that EcN ghosts was highly adherent to the intestine. Additionally, oral administration of EcN ghosts attenuated dextran sulfate sodium-induced IBD symptoms by inhibiting neutrophil chemotaxis and reactive oxygen species production in larval zebrafish. Because of the unique biological functions of EcN ghosts, it may serve as a strategy for future targeted drug delivery in IBD treatment.


Cont.
Advances in Antioxidant Applications for Combating 131I Side Effects in Thyroid Cancer Treatment

June 2023

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36 Reads

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5 Citations

Toxics

Thyroid cancer is the most common endocrine cancer, and its prevalence has been increasing for decades. Approx. 95% of differentiated thyroid carcinomas are treated using 131iodine (131I), a radionuclide with a half-life of 8 days, to achieve optimal thyroid residual ablation following thyroidectomy. However, while 131I is highly enriched in eliminating thyroid tissue, it can also retain and damage other body parts (salivary glands, liver, etc.) without selectivity, and even trigger salivary gland dysfunction, secondary cancer, and other side effects. A significant amount of data suggests that the primary mechanism for these side effects is the excessive production of reactive oxygen species, causing a severe imbalance of oxidant/antioxidant in the cellular components, resulting in secondary DNA damage and abnormal vascular permeability. Antioxidants are substances that are capable of binding free radicals and reducing or preventing the oxidation of the substrate in a significant way. These compounds can help prevent damage caused by free radicals, which can attack lipids, protein amino acids, polyunsaturated fatty acids, and double bonds of DNA bases. Based on this, the rational utilization of the free radical scavenging function of antioxidants to maximize a reduction in 131I side effects is a promising medical strategy. This review provides an overview of the side effects of 131I, the mechanisms by which 131I causes oxidative stress-mediated damage, and the potential of natural and synthetic antioxidants in ameliorating the side effects of 131I. Finally, the disadvantages of the clinical application of antioxidants and their improving strategies are prospected. Clinicians and nursing staff can use this information to alleviate 131I side effects in the future, both effectively and reasonably.


Citations (17)


... Studies have demonstrated that PEITC effectively disrupts the membrane properties of several bacteria, triggers bacterial stress responses, and impacts biofilm development by disrupting quorum-sensing systems (Borges et al., 2014(Borges et al., , 2015Kaiser et al., 2017;Krause et al., 2021). Moreover, PEITC has shown promise as an anticancer agent by inhibiting tumor cell proliferation, migration, invasion, and metastasis, while also inducing apoptosis through various signaling pathways (Dai et al., 2016;Du et al., 2024;Jeong et al., 2017;Lai et al., 2010;Lee et al., 2015;Yang et al., 2010). PEITC can also induce S-phase cell cycle arrest, decrease mitochondrial transmembrane potential, cause DNA damage, and activate Caspase-3, underscoring its broad therapeutic potential in cancer treatment (Du et al., 2024). ...

Reference:

Effects of microencapsulated phenethyl isothiocyanate on gastrointestinal cancer cells and pathogenic bacteria
Phenethyl isothiocyanate inhibits the carcinogenic properties of hepatocellular carcinoma Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways
  • Citing Article
  • June 2024

... This study shows that long-term exposure to PS-NPs induces oxidative stress and hormone imbalance through the regulation of the LHR/cAMP/PKA/STAR pathway, causing hormone imbalance by inhibiting key hormone synthesis genes, thus blocking the production of steroid hormones. The delayed synthesis of steroid hormones leads to delayed gonadal development and various pathological phenomena, and eventually leads to a de- [42]; (B) three main mechanisms; (C) interaction of behavioral changes and reproductive toxicity in zebrafish [11]; (D) potential effects on human reproduction. NPs, Nanoplastics; PS-NPs, Polystyrene nanoplastics; BPA, Bisphenol A; CAT, Catalase; MDA, Malondialdehyde; TNF-α, Tumor necrosis fac-tor-alpha; AChE, Acetylcholinesterase; E2, Estradiol; VTG, Vitellogenin; T, Testosterone; vtg2, Vitellogenin 2; cyp19a, Cytochrome P450 19A; lhb, Luteinizing hormone beta; cyp17, Cytochrome P450 17; erα, Estrogen receptor alpha; vtg1, Vitellogenin 1; cyp19b, Cytochrome P450 19B; fshr, Follicle-stimulating hormone receptor; ar, Androgen receptor. ...

Behavioral Studies of Zebrafish Reveal a New Perspective on the Reproductive Toxicity of Micro- and Nanoplastics

Toxics

... The cellular and molecular mechanisms behind insufficient oxygen supply may vary among different conditions; however, they all share the common aspect that the organism cannot deliver the right amount of molecular oxygen produced during photosynthesis to tissues. Given this impairment, over the last decade, several research groups worldwide have proposed that photosynthetic microorganisms could be used as direct local oxygen delivery systems to hypoxic tissues (Dawiec-Liśniewska et al. 2022;de Andrade et al.. 2022), including skin wounds (Obaid et al. 2021), myocardial infarction (Cohen et al. 2017), and tumors (Ma et al. 2024). Moreover, in recent years, the use of such photosynthetic cells for intravascular tissue oxygenation has also been explored, representing a potentially groundbreaking emerging technology still in its early stages. ...

Recent Advances in Living Algae Seeding Wound Dressing: Focusing on Diabetic Chronic Wound Healing

... The connection is achieved through a complex network involving the nervous system (vagus nerve and enteric nervous system) and immune, vascular, and hormonal signals [45]. The MGB axis and intestinal dysbiosis have been implicated in various neurological conditions, including autism spectrum disorder, cerebrovascular disease, Alzheimer's disease, and Parkinson's disease [6,16,59,61]. In patients with migraine, GM profiles are very different from those of healthy subjects [21,24,47,61]. ...

Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential

Aging and Disease

... Cell-derived biomimetic vectors (cell membranes, EVs, cell walls, etc.) may avoid the above defects. Compared with synthetic nanoparticles (NPs), cell-derived derivatives have superior biological functions, such as immune escape, targeting to specific cells or tissues, selective binding of harmful molecules or pathogens, and immune regulation [10], as well as good biocompatibility and degradability, which is due to their retention of the characteristics of the source cells. Compared with living cells, biomimetic materials such as EVs have a long storage time, smaller volume, and lower immunogenicity and toxic side effects [11]. ...

Cell membrane nanomaterials composed of phospholipids and glycoproteins for drug delivery in inflammatory bowel disease: A review
  • Citing Article
  • August 2023

International Journal of Biological Macromolecules

... Leakage of inclusions also occurs, resulting in apoptosis and achieving the effect of algal inhibition [94]. Due to changes in the permeability of the cell membrane, the cell membrane is prone to take up nutrients from the environment, and exceeding the threshold of the cell membrane will destroy the cell membrane [95]. Para-hydroxybenzoic acid can cause a significant increase in the production of oxygen radicals in algal cells, and free radicals such as O 2− can quickly react with cell membrane components, causing damage to the cell membrane and ultimately leading to cell death [96]. ...

The potential of white-rot fungi for algal control: Mechanisms, Strategies, and Challenges
  • Citing Article
  • July 2023

Environmental Research

... 5 However, these medications may lead to side effects. 6,7 And the high cost of long-term treatment is difficult to afford for UC patients. 8 Therefore, there is a growing focus on natural remedies and alternative therapies for UC. ...

Escherichia coli Nissle 1917 ghosts alleviate inflammatory bowel disease in zebrafish
  • Citing Article
  • July 2023

Life Sciences

... However, because it is a preliminary one, further research is required with the use of other experimental models, possibly other species, and with the examination of other biological molecules, such as DNA and proteins. As natural anti-oxidants have recently been recommended to eliminate the toxic effects of radioiodine used in the treatment of thyroid cancer [29], 17β-estradiol should be considered as a prominent candidate applied in studies on protection against the damaging effects caused by radioiodine or by other kinds of treatment. However, taking into account the potential pro-oxidative, and, therefore, unfavorable, action of 17β-estradiol, its simultaneous application with other anti-oxidants should be considered in future studies, especially since a cumulative protective effect of two anti-oxidant indole substance has recently been observed in the thyroid gland [30]. ...

Advances in Antioxidant Applications for Combating 131I Side Effects in Thyroid Cancer Treatment

Toxics

... Both larval and adult zebrafish have been effectively utilized for compound screening and toxicological testing. Zebrafish possess metabolic organs similar to humans, including the kidney and liver [14]. Consequently, researchers have successfully developed zebrafish models that mimic human pathologies, including DM [9]. ...

Advances in the Utilization of Zebrafish for Assessing and Understanding the Mechanisms of Nano-/Microparticles Toxicity in Water

Toxics