A systematic review on the impact of micro-nanoplastics on human health: Potential modulation of epigenetic mechanisms and identification of biomarkers.

Epigenetic-mediated modifications, induced by adverse environmental conditions, significantly alter an organism's physiological mechanisms. Even after elimination of the stimulus, these epigenetic modifications can be inherited through mitosis, thereby triggering transgenerational epigenetics. Plastics, with their versatile properties, are indispensable in various aspects of daily life. However, due to mismanagement, plastics have become so ubiquitous in the environment that no ecosystem on Earth is free from micro-nanoplastics (MNPs). This situation has raised profound concerns regarding their potential impact on human health. Recently, both in vivo animal and in vitro human cellular models have shown the potential to identify the harmful effects of MNPs at the genome level. The emerging epigenetic impact of MNP exposure is characterized by short-term alterations in chromatin remodelling and miRNA modulation. However, to understand long-term epigenetic changes and potential transgenerational effects, substantial and more environmentally realistic exposure studies are needed. In the current review, the intricate epigenetic responses, including the NHL-2-EKL-1, NDK-1-KSR1/2, and WRT-3-ASP-2 cascades, wnt-signalling, and TGF- ß signalling, established in model organisms such as C. elegans, mice, and human cell lines upon exposure to MNPs, were systematically examined. This comprehensive analysis aimed to predict human pathways by identifying human homologs using databases and algorithms. We are confident that various parallel miRNA pathways, specifically the KSR-ERK-MAPK pathway, FOXO-Insulin cascade, and GPX3-HIF-α in humans, may be influenced by MNP exposure. This influence may lead to disruptions in key metabolic and immune pathways, including glucose balance, apoptosis, cell proliferation, and angiogenesis. Therefore, we believe that these genes and pathways could serve as potential biomarkers for future studies. Additionally, this review emphasizes the origin, dispersion, and distribution of plastics, providing valuable insights into the complex relationship between plastics and human health while elaborating on the epigenetic impacts.

A study of forensic genetics: ITO index distribution and kinship judgment between two individuals.

According to Mendel's law of genetic separation, there must be a certain blood relationship between members of the same family, and two individuals with blood relations must have the following three situations, that is, there are two homologous genes (I denotes), one homologous gene (T denotes), and no homologous genes (O denotes), which is the ITO index for calculating the blood relationship between two individuals. The AGGU Expressmarker 22 kit, ABI 3500 genetic analyzer, and GeneMapper ID-X v1.5 software were used to statistically analyze the ITO index of the gene locus of 5 kinds of samples, 28 pairs of monozygotic twins (MT), 4,000 pairs of parent-offspring (PO), 392 pairs of full sibling (FS), 138 pairs of half-siblings (HS) (including grandchildren, uncles, and nephews) and 3,500 pairs of unrelated individuals (UI). Observing the median distribution of ITO index found that from MT, PO, FS, HS to UI, the more distant the kinship, the smaller the ITO index. Full sibling index (FSI)/half-sibling index (HSI) ≥ 1 can be used as the FS discriminant standard, FSI/HSI < 1 can be used as the HS discriminant standard. According to the distance of kinship, from the direction of MT, PO, FS, HS, and UI, the proportion of the maximum ITO index of the same type of sample in the true kinship index item showed a decreasing trend. ITO index is an important statistical means to identify the kinship between two individuals, according to which the ITO index can accurately determine the kinship between individuals, which has high application value. MT index is not 0 to identify relatives as MT, PO index is an important indicator to distinguish between relatives as PO and FS. The critical values of ITO index discriminant values for UI and HS need to be further studied.

Qizhi Zhoufei Granule Alleviate Chronic Obstructive Pulmonary Disease by Regulating Th1/Th2 Immunologic Balance Through Notch Signaling Pathway / 世界科学技术-中医药现代化

Objective To investigate the role of homologous genes absent from the wings of drosophila melanogaster(Notch)signaling pathway in the imbalance of helper T cells 1(Th1)and helper T cells 2(Th2)and the intervention mechanism of Qizhi Zhoufei Granule in chronic obstructive pulmonary disease(COPD).Methods Ten of seventy Wistar rats were selected as the blank control group,and the other rats were established by cigarette smoking combined(CS)with tracheal infusion of lipopolysaccharide(LPS).The COPD model was established by randomly selecting 3 rats in the control group and the model group to verify the success of the model.At the end of modeling,gavage administration was performed.The rats in the model group were randomly divided into model control group,positive control group(67.5 μg·kg-1)and Qizhi Zhoufei Granule high,medium and low treatment group(3.24,1.62,0.81 g·kg-1).Each group was treated with normal saline,dexamethasone acetate suspension and Qizhi Zhoufei Granule suspension at high,medium and low doses.The rats in the blank control group were given the same volume of normal saline as the model control group.After modeling with 28 days and treatment with 28 days,peak inspiratory flow(PIF)and peak expiratory flow(PEF)were detected by the animal lung function test system.Rats were killed to extract lungs,spleen,serum and bronchoalveolar lavage fluid(BALF),hematoxylin-eosin(HE)staining was used to evaluate the pathological changes of lung tissues.The level of tumor necrosis factor-α(TNF-α)in serum and BALF was determined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect Th1/Th2 cells in spleen.Immunohistochemistry(IHC)and western blot were used to detect Notch1,Hes1 and Hey1 protein levels in lung tissues.Real-time fluorescence quantitative polymerase chain reaction(Real-Time PCR)was used to detect Notch1,Hes1 and Hey1 gene expression levels in lung tissues.Result Compared with the blank control group,the lung function of the model control group was significantly decreased(P<0.05),inflammatory cell infiltration and bronchial structure destruction occurred in the lung tissue,TNF-α content in serum and BALF increased significantly(P<0.05),the percentage of spleen Th1 cells was significantly decreased(P<0.05),and the percentage of Th2 cells was significantly increased(P<0.05),the protein and mRNA expressions of Notch1,Hes1 and Hey1 in lung tissues were significantly increased(P<0.05),the differences were statistically significant;Compared with the model control group,the lung function of rats in each administration group was significantly increased(P<0.05),the pathological injury of lung tissue was alleviated,TNF-α content in serum and BALF decreased significantly(P<0.05),the percentage of spleen Th1 cells was significantly increased(P<0.05),the percentage of Th2 cells was significantly decreased(P<0.05),the lung tissue of Notch1,Hes1,Hey1 protein and mRNA expression were significantly decreased(P<0.05),the differences were statistically significant.Conclusion Qizhi Zhoufei Granule regulate Th1/Th2 balance by inhibiting Notch signaling pathway,thereby improving pulmonary function and pathological injury,and affecting immune function in COPD rats.

Influence of cyclophosphamide and its metabolites on PTEN gene after acting on ovarian cancer cell line SKOV3 / 重庆医学

Objective To study the effect of cyclophosphamide(CP) and its metabolites acrolein(ACR) on PTEN gene deleted on chromosome 10 after acting on ovarian cancer cellsSKOV3.Methods Different concentrations of CP and ACR were selected to act on recombinant PTEN protein.The phosphorylation activity of PTEN was detected by PNPP.The expression of PTEN protein was detected by Western blot.The binding mode of drug with protein was detected by the biotin combined with protein;meanwhile the expression change of P53/TP53 in PTEN gene pathway was analyzed.The target protein was obtained by immunoprecipitation(IP) after different drug concentrations acting on the cells.The phosphorylation activity of the target protein was detected by high performance liquid chromatography(HPLC).Results After the drug metabolites acting on recombinant PTEN protein,the phosphorylation activity was decreased with the increase of drug concentration,while the expression of ACR antibody action was increased with the drug concentration elevation.The expression of protein and biotin in different experimental groups was increased with the increase of drug concentration.The PTEN phosphorylation activity was decreased with the drug concentration increased in cells,and so did the expression of TP53 protein.Conclusion CP metabolite ACR induces the cytotoxicity by inhibiting PTEN protein phosphorylation activity.