Activation of ER Stress and Autophagy Induced by TDP-43 A315T as Pathogenic Mechanism and the Corresponding Histological Changes in Skin as Potential Biomarker for ALS with the Mutation

Abstract Deltamethrin (DLM) is a widely used and highly effective insecticide. DLM exposure is harmful to animal and human. Quail, as a bird model, has been widely used in the toxicology field. However, there is little information available in the literature about quail cerebrum damage caused by DLM. Here, we investigated the effect of DLM on quail cerebrum neurons. Four groups of healthy quails were assigned (10 quails in each group), respectively given 0, 15, 30, and 45 mg/kg DLM by gavage for 12 weeks. Through the measurements of quail cerebrum, it was found that DLM exposure induced obvious histological changes, oxidative stress, and neurons apoptosis. To further explore the possible molecular mechanisms, we performed real-time quantitative PCR to detect the expression of endoplasmic reticulum (ER) stress-related mRNA. In addition, we detected ATP content in quail cerebrum to evaluate the functional status of mitochondria. The study showed that DLM exposure significantly increased the expression of ER stress-related mRNA and decreased ATP content in quail cerebrum. These results suggest that chronic exposure to DLM induces apoptosis of quail cerebrum neurons via promoting ER stress and mitochondrial dysfunction. Furthermore, our results provide a novel explanation for DLM-induced apoptosis of avian cerebrum neurons.

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Potentials of neuron-specific enolase as a biomarker for gastric cancer

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i3.7 ◽

2020 ◽

Vol 19 (3) ◽

pp. 505-511

Author(s):

Lingyun Wang ◽

Ruirui Hu ◽

Hongmei Liu ◽

Wen Li ◽

Lili Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Immunohistochemical Staining ◽

Early Stage ◽

Neuron Specific Enolase ◽

Tnm Staging ◽

Enzyme Linked Immunosorbent Assay ◽

Histological Changes ◽

Potential Biomarker ◽

Number Of Patients ◽

Significant Difference

Purpose: To investigate the potentials of neuron-specific enolase (NSE) as a biomarker for gastric cancer (GC). Methods: Gastric cancer (GC) patients (n = 412) who underwent gastrectomy were recruited over a 3- year period for this study. Their clinicopathological data such as age, sex, histological type, depth, tumor invasion, lymph node metastasis, and distant metastasis were analyzed. The patients were followed up for four years and the outcomes were also assessed. Histological changes in biopsies and levels of expression of NSE in biopsies and serum of patients were determined using immunohistochemical staining, western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Results: Immunohistochemical staining showed that NSE was differentially expressed in the cytoplasm of GC cells. Histological changes in biopsies of patients in the overexpression group were not significantly different from those of patients in under-expression group (p > 0.05). In NSE overexpression group, the number of patients in early stage GC subgroup (n = 186, 86.10 %, T1) were significantly higher than that in advanced GC subgroup (n = 124, 62.20 % T2–T4) (p < 0.05). However, in NSE under-expression group, there were more patients in advanced GC subgroup (n = 72, 37.70 %) than in early GC subgroup (n = 30, 13.80 %) (p < 0.05). Patients in NSE overexpression group survived longer than those in NSE under-expression group (p < 0.05). The level of expression of NSE significantly decreased with increase in TNM stage (p < 0.05). There was no significant difference in serum NSE level between GC patients and healthy control (p > 0.05). The results of the correlation analysis indicated that NSE levels were positively associated with GC. Conclusion: The results obtained in this study suggest that NSE could serve as a potential biomarker for GC. Keywords: Biomarker, Gastric cancer, Neuron-specific enolase, Overexpression, TNM staging

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Targeting NAT10 Induces Apoptosis Associated With Enhancing Endoplasmic Reticulum Stress in Acute Myeloid Leukemia Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.598107 ◽

2020 ◽

Vol 10 ◽

Author(s):

Jie Zi ◽

Qi Han ◽

Siyu Gu ◽

Mary McGrath ◽

Shriya Kane ◽

...

Keyword(s):

Cell Cycle ◽

Acute Myeloid Leukemia ◽

Er Stress ◽

Cell Cycle Arrest ◽

Myeloid Leukemia ◽

Specific Inhibitor ◽

Cycle Arrest ◽

Potential Biomarker ◽

Upr Pathway ◽

Acute Myeloid

N-acetyltransferase 10 (NAT10) has oncogenic properties in many tumors through its role in different cellular biological processes. NAT10 is also a potential biomarker in acute myeloid leukemia (AML); however, the mechanisms underlying NAT10’s contribution to disease states and the effect of targeting NAT10 as a therapeutic target remain unclear. NAT10 was found to be highly expressed in patients with AML, and increased NAT10 expression was associated with poor outcomes. Additionally, targeting NAT10 via the shRNA knockdown and its pharmacotherapeutic inhibitor resulted in inhibition of cell proliferation, induction of cell cycle arrest in the G1 phase, and apoptosis in AML cells. Moreover, NAT10 induces cell cycle arrest by decreasing expression of CDK2, CDK4, CyclinD1, Cyclin E while simultaneously increasing the expression of p16 and p21. Targeting NAT10 induces ER stress through the increased expression of GRP78 and the cleavage of caspase 12, which are classical markers of ER stress. This triggered the Unfolded Protein Response (UPR) pathway by consequently increasing IRE1, CHOP, and PERK expression, all of which play crucial roles in the UPR pathway. Targeting NAT10 also activated the classical apoptotic pathway through the upregulation of the Bax/bak and the concurrent downregulation of Bcl-2. In summary, our data indicate that targeting NAT10 promotes ER stress, triggers the UPR pathway, and activates the Bax/Bcl-2 axis in AML cells. Our results thus indicate a novel mechanism underlying the induction of NAT10 inhibition-mediated apoptosis and reveal the potential for the therapeutic effect of a NAT10 specific inhibitor in AML.

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Chronic Laser Exposure Effects on Rabbit Retina

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100093523 ◽

1972 ◽

Vol 30 ◽

pp. 54-55

Author(s):

Burton B. Silver ◽

Theodore Lawwill

Keyword(s):

Laser Irradiation ◽

Laser Light ◽

Broad Band ◽

Argon Laser ◽

Atropine Sulfate ◽

Ultrastructural Changes ◽

Laser Exposure ◽

Rabbit Retina ◽

Histological Changes ◽

Threshold Doses

Dutch-belted 1 to 2.5 kg anesthetized rabbits were exposed to either xenon or argon laser light administered in a broad band, designed to cover large areas of the retina. For laser exposure, the pupil was dilated with atropine sulfate 1% and pheny lephrine 10%. All of the laser generated power was within a band centered at 5145.0 Anstroms. Established threshold for 4 hour exposures to laser irradiation are in the order of 25-35 microwatts/cm2. Animals examined for ultrastructural changes received 4 hour threshold doses. These animals exhibited ERG, opthalmascopic, and histological changes consistent with threshold damage.One month following exposure the rabbits were killed with pentobarbitol. The eyes were immediately enucleated and dissected while bathed in 3% phosphate buffered gluteraldehyde.

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The miR-21 potential of serving as a biomarker for liver diseases in clinical practice

Biochemical Society Transactions ◽

10.1042/bst20200653 ◽

2020 ◽

Vol 48 (5) ◽

pp. 2295-2305

Author(s):

Jiawei Zhang ◽

Dandan Li ◽

Rui Zhang ◽

Peng Gao ◽

Rongxue Peng ◽

...

Keyword(s):

Clinical Practice ◽

Liver Diseases ◽

Hepatic Disease ◽

Noninvasive Detection ◽

Diagnosis And Prognosis ◽

Expected Performance ◽

Potential Biomarker ◽

Disease Condition ◽

Complex Regulatory Network

The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.

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Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population

VASA ◽

10.1024/0301-1526/a000348 ◽

2014 ◽

Vol 43 (3) ◽

pp. 189-197 ◽

Cited By ~ 10

Author(s):

Yiqiang Zhan ◽

Jinming Yu ◽

Rongjing Ding ◽

Yihong Sun ◽

Dayi Hu

Keyword(s):

High Density Lipoprotein ◽

Total Cholesterol ◽

High Density Lipoprotein Cholesterol ◽

Ankle Brachial Index ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Cholesterol Ratio ◽

Potential Biomarker

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.

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