Soil heavy metal pollution has become a worldwide environmental issue that has attracted considerable public attention, largely from the increasing concern for the security of agricultural products. ...Heavy metals refer to some metals and metalloids possessing biological toxicity, such as cadmium, mercury, arsenic, lead, and chromium. These elements enter the soil agro-ecosystem through natural processes derived from parent materials, and through anthropogenic activities. Heavy metal pollution poses a great threat to the health and well-being of organisms and human beings due to potential accumulation risk through the food chain. Remediation using chemical, physical, and biological methods has been adopted to solve the problem. Phytoremediation has proven to be a promising alternative to conventional approaches as it is cost effective, environmentally friendly, and aesthetically pleasing. To date, based on the natural ability of extraction, approximately 500 taxa have been identified as hyperaccumulators of one or more metals. In addition, further research integrating biotechnological approaches with comprehensive multidisciplinary research is needed to improve plant tolerance and reduce the accumulation of toxic metals in soils. This review discusses harmful effects, sources of heavy metals, and the remediation technologies for soil contaminated by heavy metals.
Ferroptosis is a type of non-apoptotic regulated cell death that involves excessive iron accumulation and subsequent lipid peroxidation. Although the antioxidant mechanisms of ferroptosis have been ...extensively studied recently, little is known about the interactions between the different organelles that control ferroptosis. Here, we show that the translocation of lysosomal cysteine protease cathepsin B (CTSB) into the nucleus is an important molecular event that mediates organelle-specific initiation of ferroptosis in human pancreatic cancer cells. Iron-dependent lysosomal membrane permeability triggers the release of CTSB from the lysosome to nucleus during ferroptosis. Mechanistically, nuclear CTSB accumulation causes DNA damage and subsequent activation of the stimulator of interferon response CGAMP interactor 1 (STING1/STING)-dependent DNA sensor pathway, which ultimately leads to autophagy-dependent ferroptosis. Consequently, the genetic inhibition of CTSB-dependent STING1 activation by RNAi prevents ferroptosis in cell culture and animal models. These new findings not only enhance our understanding of the mechanism by which organelles specifically trigger ferroptosis, but also may provide a potential way to enhance the anticancer activity of ferroptosis therapy.
•Increased CTSB expression, activity, and translocation during ferroptosis•CTSB triggers DNA damage and STING1 activation during ferroptosis•CTSB mediates autophagy-dependent ferroptosis•CTSB regulates ferroptosis therapy in vivo
This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and ...corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Lucif-erase reporter plasmids were prepared to evaluate the transduction activity of Wnt/β-catenin signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, over-expressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (
< 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (
< 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (
< 0.05), and miR-29b-3p also bound to PGRN in a direct manner (
< 0.05). Finally, addition of LiCl (Wnt/β-catenin pathway activator) or XAV93920 (Wnt/β-catenin pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of β-catenin/Tcf reporter plasmid (
< 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.
Abstract
Background
Type 2 diabetes mellitus is an expanding global public health issue, especially in developing countries. This study aimed to investigate the prevalence, awareness and control rate ...of type 2 diabetes mellitus, and assess its risk factors in elderly Chinese individuals.
Methods
The health screening data of 376,702 individuals aged ≥ 65 years in Wuhan, China, were collected to analyse the prevalence, awareness, and control rates of diabetes. Indices, including fasting plasma glucose and other biochemical indicators, were measured for all participants using standard methods at the central laboratory. Multilevel logistic regression analysis was performed to assess the key determinants of the prevalence, awareness, and control rates of diabetes.
Results
The prevalence, awareness, and control rates of diabetes in the Chinese individuals aged ≥ 65 years were 18.80%, 77.14%, and 41.33%, respectively. There were statistically significant differences in the prevalence, awareness, and control rates by gender. Factors associated with diabetes prevalence were age, body mass index (BMI), and central obesity; while those associated with awareness and control were gender, education level, marital status, physical activity, alcohol consumption, BMI, and central obesity.
Conclusions
Diabetes is an important public health problem in the elderly in China. The awareness and control rates have improved, but overall remained poor. Therefore, effective measures to raise awareness and control the rates of diabetes should be undertaken to circumvent the growing disease burden in elderly Chinese people.
Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These components include the extracellular matrix, fibroblasts, immune cells, and ...endothelial cells. In the early stages of tumors, the tumor microenvironment has a tumor suppressor function. As the tumor progresses, tumor immune tolerance is induced under the action of various factors, such that the tumor suppressor microenvironment is continuously transformed into a tumor-promoting microenvironment, which promotes tumor immune escape. Eventually, tumor cells manifest the characteristics of malignant proliferation, invasion, metastasis, and drug resistance. In recent years, stress effects of the extracellular matrix, metabolic and phenotypic changes of innate immune cells (such as neutrophils, mast cells), and adaptive immune cells in the tumor microenvironment have been revealed to mediate the emerging mechanisms of immune tolerance, providing us with a large number of emerging therapeutic targets to relieve tumor immune tolerance. Gastric cancer is one of the most common digestive tract malignancies worldwide, whose mortality rate remains high. According to latest guidelines, the first-line chemotherapy of advanced gastric cancer is the traditional platinum and fluorouracil therapy, while immunotherapy for gastric cancer is extremely limited, including only Human epidermal growth factor receptor 2 (HER-2) and programmed death ligand 1 (PD-L1) targeted drugs, whose benefits are limited. Clinical experiments confirmed that cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular endothelial growth factor receptor (VEGFR) and other targeted drugs alone or in combination with other drugs have limited efficacy in patients with advanced gastric cancer, far less than in lung cancer, colon cancer, and other tumors. The failure of immunotherapy is mainly related to the induction of immune tolerance in the tumor microenvironment of gastric cancer. Therefore, solving the immune tolerance of tumors is key to the success of gastric cancer immunotherapy. In this study, we summarize the latest mechanisms of various components of the tumor microenvironment in gastric cancer for inducing immune tolerance and promoting the formation of the malignant phenotype of gastric cancer, as well as the research progress of targeting the tumor microenvironment to overcome immune tolerance in the treatment of gastric cancer.
Programmed death-ligand 1 (PD-L1) is a promising target of cancer immune therapy. It not only expressed in tumor cells (TCs) but also up regulated in tumor infiltrating immune cells (TIICs). Although ...the previous meta-analysis have shown that PD-L1 expression in TCs was a valuable biomarker in predicting cancer prognosis, but few researches systematic evaluated the association between its expression in TIICs and survival of cancer patients. Thus, we performed this meta-analysis to evaluate the prognostic value of PD-L1 expression in TIICs in different types of cancers. Our results are valuable supplements when using PD-L1 expression to predict the survival of cancer patients and to select the beneficial patients from PD-L1 target therapy. PubMed, Embase, Web of Science and the Cochrane Central Search Library were used to perform our systematic literature search. Overall survival (OS) at 5th years and hazard ratios (HRs) were calculated using random effects models. Eighteen studies involving 3674 patients were included. The median positive rate of PD-L1 staining in TIICs was 36.37%. PD-L1 positive expression in TIICs related to a lower risk of death (HR = 0.784, 95%CI: 0.616-0.997, P = 0.047). Subgroup analyses found that PD-L1 positive expression in TIICs indicated a better prognosis especially in breast cancer patients (HR = 0.359, P = 0.041). When using whole tissue section slides, or using 'any expression in TIICs' as a cutoff value to assessing the results of IHC staining, PD-L1 expression in TIICs had a good prognostic value in cancer prognosis (HR = 0.587, P = 0.001 and HR = 0.549, P = 0.002). Our findings suggested that PD-L1 expression in TIICs was related to a better survival of cancer. The comprehensive evaluation of tumor cells and tumor infiltrating immune cells are required when evaluating the effect of PD-L1 expression on prognosis of cancer in future research.
Numerical simulation of oil-water miscible displacement is discussed in this paper, and a compressible problem of energy mathematics is solved potentially. The mathematical model defined by a ...nonlinear system includes mainly two partial differential equations (PDEs): a parabolic equation for the pressure and a convection-diffusion equation for the saturation. The pressure is obtained by a conservative mixed finite volume element method (MFVE). The computational accuracy is improved for Darcy velocity. A conservative upwind mixed finite volume element method (UMFVE) is applied to compute the saturation on changing meshes. The diffusion is discretized by a mixed finite volume element method, and the convection is computed by upwind differences. The upwind method can solve convection-dominated diffusion equations accurately and avoids numerical dispersion and nonphysical oscillation. The saturation and the adjoint vector function are obtained simultaneously. An optimal order error estimates is obtained. Finally, numerical examples are provided to show the accuracy, efficiency and possible applications.
Ferroptosis is a type of iron-dependent regulated cell death caused by the disruption that occurs when oxidative stress and antioxidant defenses interact, and then driven by lipid peroxidation and ...subsequent plasma membrane ruptures. The regulation of ferroptosis involves many factors, including the crosstalk between subcellular organelles, such as mitochondria, endoplasmic reticulum (ER), lysosomes, lipid droplets, and peroxisomes. Here, we show that the ER protein STING1 (also known as STING or TMEM173) promotes ferroptosis in human pancreatic cancer cell lines by increasing MFN1/2-dependent mitochondrial fusion, but not mitophagy-mediated mitochondrial removal. The classic ferroptosis inducer erastin, but not sulfasalazine, induces the accumulation of STING1 in the mitochondria, where it binds to MFN1/2 to trigger mitochondrial fusion, leading to subsequent reactive oxygen species production and lipid peroxidation. Consequently,
in vitro
or xenograft mouse models show that the genetic depletion of STING1 or MFN1/2 (but not the mitophagy regulator PINK1 or PRKN) reduces the sensitivity of pancreatic cancer cells to ferroptosis. These findings not only establish a new mitochondrial fusion-dependent cell death mechanism, but also indicate a potential strategy for enhancing ferroptosis-based therapy.
Pancreatic cancer is an aggressive malignancy with changes in the tumor microenvironment. Here, we demonstrate that PINK1 and PARK2 suppressed pancreatic tumorigenesis through control of ...mitochondrial iron-dependent immunometabolism. Using mouse models of spontaneous pancreatic cancer, we show that depletion of Pink1 and Park2 accelerates mutant Kras-driven pancreatic tumorigenesis. PINK1-PARK2 pathway-mediated degradation of SLC25A37 and SLC25A28 increases mitochondrial iron accumulation, which leads to the HIF1A-dependent Warburg effect and AIM2-dependent inflammasome activation in tumor cells. AIM2-mediated HMGB1 release further induces expression of CD274/PD-L1. Consequently, pharmacological administration of mitochondrial iron chelator, anti-HMGB1 antibody, or genetic depletion of Hif1a or Aim2 in pink1−/− and park2−/− mice confers protection against pancreatic tumorigenesis. Low PARK2 expression and high SLC25A37 and AIM2 expression are associated with poor prognosis in patients with pancreatic cancer. These findings suggest that disrupted mitochondrial iron homeostasis may contribute to cancer development and hence constitute a target for therapeutic intervention.
Display omitted
•PINK1 and PARK2 suppress oncogenic Kras-driven pancreatic tumorigenesis•Mitochondrial iron accumulation contributes to pancreatic tumorigenesis•HIF1A is required for the Warburg effect in pancreatic tumorigenesis•AIM2-mediated HMGB1 release promotes pancreatic tumorigenesis
Li et al. demonstrate in mouse models that Pink1 and Park2 deficiency accelerates pancreatic tumorigenesis through mitochondrial iron-dependent immunometabolic dysfunction. These findings shed light on how the autophagy pathway controls iron homeostasis and could have implications for the development of strategies to target mitochondrial iron metabolism in pancreatic cancer.
If esophageal papilloma (EP) is a rare condition, esophageal papillomatosis (EPS) is a distinct rarity. To date, only 53 well documented cases have been described in English literature. However, the ...number of reports on EPS significantly increased to over 40 cases during the past 20 years. Perhaps, this is due to the broad use of endoscopy and related research achievements. Most of the cases are individual and it seems that there are no associations between them. And up to now no guidelines can be followed. To further understand this exceedingly rare disease, we had a comprehensive review of the epidemiology, etiology, clinical manifestations, pathogenesis, treatment, and clinical course of EPS.
PDF
