Journal of Environmental Pathology Toxicology and Oncology最新文献

Toxicity caused by heavy metals inflicts a grave global menace to the habitat and inhabitants. Arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) are the non-essential yet harmful heavy metals commonly associated with pollution and resultant health complications. Typical chelating/complexing agents are not worthy of combating heavy metal-induced sub-chronic and chronic toxicities. It transpires from scientific data mining that, honey obviates investigational heavy metal toxicity. This review aims to collate such investigations conducted against As, Cd, and Pb toxicity. There is a total of 19 pre-clinical works demonstrating the ameliorative effect of honey against empirical As, Cd, and Pb toxicity. Pre-clinical reports against Hg and clinical study against these heavy metals could not found. From the outcome of the current literature investigation, it seems that honey has a marked heavy metal toxicity meliorative effect which is chiefly ascribed to its innate antioxidant effect due to its diverse polyphenol content.

The purpose of the present study was to investigate the potentials of circ_0000311 in oral squamous cell carcinoma (OSCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for calculating the mRNA and miRNA level. Western blot was performed to determine protein expression. The binding sites between miR-876-5p and circ_0000311/Enhancer of zeste homolog-2 (EZH2) were predicted using bioinformatics tools and confirmed by luciferase and RNA pull-down assays. Cell proliferation was detected using CCK-8 and colony formation assay. Cell migration and invasion were detected using transwelll assay. Cellular functions were determined using CCK-8, colony, and transwell assay. The results showed that circ_0000311 was overexpressed in OSCC tissues and cells. However, circ_0000311 knockdown impeded the proliferation and epithelial-mesenchymal transition (EMT) of OSCC cells. Circ_0000311 targeted miR-876-5p, down-regulation of which promoted the aggressiveness of OSCC. Additionally, circ_0000311 sponged miR-876-5p to up-regulate a key regulator of EMT EZH2, which promoted the proliferation and aggressiveness of OSCC. Taken together, circ_0000311 aggravated the OSCC progression via regulating miR-876-5p/EZH2 axis.

Gestational diabetes mellitus (GDM), a common complication in pregnancy, could threaten the health of both pregnancies and their offspring. miR-210-3p has been reported that play a crucial role in many diseases. Nevertheless, the molecular mechanism and clinical significance of miR-210-3p in the GDM is still unclear. miR-210-3p was overexpressed in the pancreas of the GDM mouse model. Meanwhile, miR-210-3p weakens cell viability and promotes the apoptosis of pancreatic β cells, impairing the function of pancreatic β cells. Bioinformatics analysis showed that miR-210-3p directly targets the expression of Dtx1, and miR-210-3p negatively regulated dtx1. Down-expression of Dtx1 could increase the expression of insulin and boost the function of pancreatic β cells through inhibiting expressions of p-Akt, p-mTOR, p-4E-BP1, and p-SGK1. Rescue experiments verified that miR-210-3p could regulate the function of pancreatic β cells and adjust the content of TG, TC, and HDL in the blood of mice with GDM via regulating the expression of Dtx1. The study demonstrated that miR-210-3p is significantly overexpressed in the pancreas of the GDM mouse model, which could impair the function and cell viability of pancreatic β cells via suppressing the expression of Dtx1 promotes the progression of GDM. These findings provide a novel strategy to treat GDM.

Inactivation of hepatic stellate cells (HSCs) slows down liver cirrhosis (LC) advancement. The role of circular RNAs (circRNAs) in LC is largely undiscovered. Here, we clarified the effect of circCHD2 on HSCs. LX-2 cells were stimulated with TGF-β1 to establish a cell model. The circCHD2, miR-200b-3p, and HLF were inspected using quantitative real-time PCR (qPCR). Cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, together with colony formation assays were all conducted to analyze cell proliferation. α-SMA and Col1A1 were evaluated by qPCR and Western blot. The targets of circCHD2 and miR-200b-3p were verified by luciferase reporter assay. We found the circCHD2 was upregulated in the patients with LC and transforming growth factor beta 1 (TGF-β1)-stimulated LX-2 cells. Interfering of circCHD2 inhibited the proliferation induced by TGF-β1, downregulated α-SMA, and Col1A1. CircCHD2 served as a miR-200b-3p sponge, which directly targeted downstream HLF. Downregulated miR-200b-3p abrogated suppression on the cellular process, α-SMA and Col1A1 levels induced by knockdown of circCHD2. Enforced HLF reversed the effect induced by miR-200b-3p overexpression. Taken together, a loss of circCHD2/miR-200b-3p/HLF axis contributed to alleviate LC progression. The findings suggested that circCHD2 may have potential to be a therapeutic target of LC.

Melatonin is primarily synthesized in the pineal gland under the influence of noradrenergic stimulation at night. It regulates the sleep-wake cycle, gonadal activity, redox homeostasis, immune functions, and anticarcinogenic effects at the normal physiological state. The activity of melatonin is mediated by membrane-bound G protein-coupled receptors MT1 and MT2. Circadian deregulation, exposure to light-at-night, shift work, and jet lag disrupt the melatonin rhythm. A low level of circulatory melatonin concentration influences the development of many cancers, including breast cancer. Melatonin acts as an anticancer agent in breast tissue. It suppresses metabolic activity, regulates cell-signaling pathways, and subsequently blocks cell proliferation. This indolamine induces apoptosis, inhibits chronic inflammation and metastasis. Melatonin restricts the functions of estrogen receptor α and also inhibits aromatase activity. Melatonin is a potent antioxidant that reduces the chemoresistance capacity of breast cancer cells. At therapeutic levels, it potentially increases the efficacy of chemotherapeutic agents and decreases their adverse effects during the treatment of breast cancer. The present review focuses on the antineoplastic activity of melatonin against breast cancer. Emphasis has been given to the possible use of melatonin in the treatment of breast cancer.

The use of platinum (Pt)-based anticancer drugs, although widespread in clinical practice, is severely limited due to toxic side-effects. One of the strategies for making Pt-based chemotherapy more effective is the synthesis and use of Pt nanoparticles (PtNPs). However, increasing evidence suggestD that nanoplatinum also pose potential risk to human health. This study examined the toxicity and anticancer activity of mycosynthesized PtNPs against sarcoma-180 (S-180) cells in vitro and in vivo. Curvularia affinis Boedijn, a phyto-pathogenic fungi isolated from rice, was used to synthesize PtNPs (named as CaPtNP). Well dispersed, mostly spherical CaPtNPs, with sizes ranging from 3-9 nm were characterized by Transmission electron microscopy (TEM), field emission scanning electron microscopy, X-ray diffraction, atomic force microscopy, and Fourier transform infrared spectrometry. Two concentrations of the CaPtNPs (2.31 and 4.63 ng/mL) were selected based on in vitro cytotoxicity assay on erythrocytes and peripheral blood mononuclear cells. The selected doses were found to induce significant in vitro and in vivo anti-proliferative and pro-apoptotic activity in S-180 cells. Elevated levels of pro-apoptotic markers (p53, Bax/Bcl2 ratio, Cyt c, caspase-3, cleaved PARP) and reduced BrdU incorporation validated the anticancer activity of CaPtNPs. The antitumor activity was further confirmed in S-180 transplanted tumor bearing mice. Moreover, examination of the impact of sub-chronic exposure (three months) of CaPtNPs on the ultra-structural features of renal and hepatic tissue by TEM revealed no significant toxicological manifestation in these organs. The CaPtNPs were also found to reduce oxidative stress and improve liver function in tumor bearing mice compared with untreated controls. Thus, this green CaPtNPs was well tolerated in mice and displayed significant antitumor property.

Breast carcinoma, one of the most lethal variants of carcinogenesis, significantly diagnosed type of cancer amongst the female population. Sinigrin, also known as glucosinolate, is found in the seeds of Brassica nigra and shown to enhance various cancer cells potentially. Nevertheless, the mechanistic explanation of sinigrin (SGN)-mediated breast cancer growth and augmentation is still to be investigated. Therefore, we contended in this study that SGN impedes PI3K/AKT/mTOR phosphorylation-mediated cell cycle arrest in MCF-7 cells. SGN (20 M) was implemented to treat MCF-7 cells for 24 and 48 hours of incubation. A significant increase in cytotoxicity, reactive oxygen species (ROS) generation, cell cycle arrest, mitochondrion membrane alteration, lipid peroxidation, and antioxidant depletion was found in MCF-7 cells. The PI3K/AKT/mTOR events are crucial pathways that participate in survival, proliferation, and cell cycle regulation. Inhibition of PI3K/AKT/mTOR expression thought to be novel approach for alleviating breast cancer growth. We noticed that SGN inhibits PI3K, AKT, and mTOR phosphorylation, resulting in the downregulation of proliferative and cell cycle regulatory proteins, such as cyclin-Dl, PCNA, CDK4, and CDK6. SGN also causes apoptosis in MCF-7 cells by increasing nuclear fragmentation and by inducing pro-apoptotic gene expression. As a result, SGN inhibits breast cancer growth by impeding PI3K/AKT/mTOR phosphorylation-mediated cell cycle arrest in MCF-7 cells.

Cervical squamous cell carcinoma (CESC) is one of the most common causes of cancer-related deaths in women. RNA modification "writers" modulate and alter RNA molecular activity and have been implicated in the origin and development of cancer. We explored the effects of RNA modification writers on the tumor microenvironment in CESC and their prognostic value. RNA modification writers were altered at the genetic and transcriptional levels in CESC sample data downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. A principal component analysis (PCA) score model was established based on the genes screened by Cox regression analysis and random forest dimensionality reduction. A survival analysis of CESC patients revealed significant differences between patients with high and low scores. The gene set variation analysis method was used for a functional enrichment analysis. The relative abundance of immune cells in CESCs was quantified using the CIBERSORT algorithm. There were significant differences in multiple signaling pathways and immune cells between the patients with high and low scores. Based on Genomics of Drug Sensitivity in Cancer data, we analyzed the genetic mutations in CESCs and predicted the therapeutic effects of multiple anticancer drugs. Patients with high scores showed significant resistance. Finally, the N-acetylgalactosaminyltransferase 2 (GALNT2) was highly expressed in CESCs and was associated with multiple immune cells and the formation of the extracellular matrix. PCA score based on RNA modification writers is closely associated with immune infiltration in the tumor microenvironment and could be used as a reference for prognosis and medication in CESC patients.

Neurodegeneration has been recognized as a clinical episode characterized by neuronal death, including dementia, cognitive impairment and movement disorder. Most of the neurodegenerative deficits, via clinical symptoms, includes common pathogenic features as protein misfolding and aggregation. Therefore, the focus highlights the cellular organelle endoplasmic reticulum (ER) critically linked with the quality control and protein homeostasis. Unfolded protein response (UPR) or ER stress have also been considered as hallmarks for neurodegenerative disorders. It has been implicated that the levels of endocannabinoids (ECB) could rise at the platform of neurodegeneration. In addition, phytocannabinoids (PCB) including cannabidiol (CBD) could also initiate the IRE1, PERK, XBP-1, and ATF6, pathways that could lead to the degradation of the misfolded proteins and termination of protein translation. Thus, our aim was to determine if cannabinoids bind to these ER arm proteins involved in UPR by molecular docking and therefore determine its drug resemblance through ADME analysis. In our study, three cannabinoid receptors (CB1, CB2, and CB3) were considered to demonstrate their neuroprotective actions. The chosen ligands were screened as PCB (Δ9-tetrahydrocannabinol or THC), CBD, and two ECB, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The current findings have advocated that the cannabinoids and their molecular targets have shown considerable binding and their ADME properties also reveals that they possess moderate drug-like properties making it as a valuable option for the treatment and management of neurodegenerative diseases.

Bladder urothelial carcinoma (BLCA) is estimated to cause approximately 150,000 deaths per year worldwide. The prognosis of BLCA remains dismal, so early detection can have a significant impact on clinical outcomes. Numerous studies have shown that genes can alter the progression of tumors by regulating cell cycle, thus achieving targeted therapy. A comprehensive comparison analysis of expression profiles in BLCA datasets downloaded from Gene Expression Omnibus (GEO) was conducted to identify common differentially expressed genes (DEGs) using R packages. Gene Set Enrichment Analysis (GSEA) of identified DEGs was performed, and a protein-protein interaction (PPI) network was mapped using Cytoscape software. The expression of hub genes was validated in GEPIA2, cBioPortal, and ONCOMINE databases. The potential roles of the cell cycle genes (CCGs) in immunity were also explored. A total of 70 DEGs from GSE13507, GSE37815, and GSE52519 were identified commonly, including 23 up-regulated and 47 down-regulated genes. GSEA and PPI analysis revealed genes in the cell cycle pathway significantly enriched in tumor tissues, and the expression of 12 CCGs was up-regulated. Furthermore, significant differences of the CCGs expression were found in different immune subtypes of BLCA. The expression of CCGs was closely related to CD4+ T cell, memory B cell, eosinophil, monocyte, T helper cell, and many marker genes of immunomodulators. Abundance of tumor-infiltrating lymphocytes were associated with patients' overall survival with BLCA. Increased CCG expression was correlated with better prognosis in BLCA patients, together with higher immune infiltration levels in CD4 T activated memory cell, and CD8 T central cell, respectively. The up-regulated CCGs in BLCA tumor tissues played important roles in immune cell infiltration and could be novel targets for tumor immunotherapy in BLCA.