MicroRNA-Mediated Calcineurin Signaling Activation Induces CCL2, CCL3, CCL5, IL8 and Chemotactic Activities in 4,4’-Methylene Diphenyl Diisocyanate Exposed Macrophages

Xenobiotica ◽  
2021 ◽  
pp. 1-20
Author(s):  
Chen-Chung Lin ◽  
Brandon F. Law ◽  
Justin M. Hettick
Keyword(s):  
Methylene Diphenyl Diisocyanate ◽  
Signaling Activation ◽  
Calcineurin Signaling

Evaluation of respiratory exposure to 4,4-methylene diphenyl diisocyanate (MDI) vapors in foam injection workers in a household appliance manufacturing company: An Occupational Carcinogen

2019 ◽  
Vol 2 (1) ◽  
pp. 23-27
Author(s):  
Ahmad Nikpey ◽  
Hamzeh Saeidabadi ◽  
Salman Sheikhi ◽  
Saeed Yari ◽  
Tayyebeh Jaddi Madarsara
Keyword(s):  
Ventilation System ◽  
The Body ◽  
Foam Material ◽  
Respiratory Capacity ◽  
Household Appliance ◽  
Administrative Personnel ◽  
Respiratory Exposure ◽  
Methylene Diphenyl Diisocyanate ◽  
Manufacturing Company ◽  
Spss Software

Background: Appliance manufacturing boom is very high hand customers always have a great deal of attention to products that have low energy consumption, therefore the use of isocyanates MDI as a thermal insulation in the body of the refrigerator and is also widely used as a binder in the production of washing machines.  MDI isocyanate study the effects on the respiratory capacity of formers injection was done foam material in a household appliance company Method: this case control study in 1395 and a household appliance manufacturing company in the province of Qazvin 20 personnel working injected foam material is exposed to isocyanates ,for example administrative personnel and 20 served as controls using medical records these values breathing capacity  FVC , FEV1 , FEV1/FVC in  both 1390 and 1394 extracted using SPSS software and paired T-TEST data were analyzed. Results: Measuring the concentration of isocyanate in 90 blocks in the cabin and tap lid above the limit, which was due to the failure of the ventilation system, in 94 years due to the good performance of the ventilation system in the isocyanate concentration was at the limit. According to their experiences foam material is injected every three indexes FVC, FEV1, FEV1/FVC had significant losses, FEV1 and FVC decline among which were a significant level. (p=0.036, p= 0.008) the control samples also non- significant decline in the indicators that this can be attributed to aging. Conclusion: It is known that exposure to isocyanate materials decreased respiratory capacity is personnel, to postpone it to the desired function ventilation system. it would be desirable to postpone the operation of the ventilation system and non-isocyanate leak on the ground, work, be a lot of attention. even with the improvement of the job must be conservative’s injection foam material is exposed to isocyanates be included in the list of hard and hazardous jobs.   Keywords: MDI, respiratory exposure, respiratory capacity, workers inject foam material.

Minocycline inhibits mTOR signaling activation and alleviates behavioral deficits in the Wistar rats with acute ischemia stroke

2020 ◽  
Vol 19 ◽  
Author(s):  
Shengyuan Wang ◽  
Chuanling Wang ◽  
Lihua Wang ◽  
Zhiyou Cai
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Acute Ischemia ◽  
Intragastric Administration ◽  
Underlying Mechanisms ◽  
Signaling Activation ◽  
The Brain ◽  
Minocycline Therapy

Background: Mammalian target of rapamycin (mTOR) has been evidenced as a multimodal therapy in the path-ophysiological process of acute ischemic stroke (AIS). However, the pathway that minocycline targets mTOR signaling is not fully defined in the AIS pathogenesis. This study is to aim at the effects of minocycline on the mTOR signaling in the AIS process and further discover the underlying mechanisms of minocycline involved in the following change of mTOR signaling-autophagy. Methods: Cerebral ischemia/reperfusion (CIR) rat animal models were established with the transient suture occlusion into middle cerebral artery. Minocycline (50mg/kg) was given by intragastric administration. The Morris water maze was used to test the cognitive function of animals. Immunohistochemistry and immunofluorescence were introduced for testing the lev-els of synaptophysin and PSD-95. Western blot was conducted for investigating the levels of mTOR, p-mTOR (Ser2448), p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366), p-eIF4B (Ser406), LC3, p62, synaptophysin and PSD-95. Results: Minocycline prevents cognitive decline of the MCAO stroke rats. Minocycline limits the expression of p-mTOR (Ser2448) and the downstream targets of mTOR [p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366) and p-eIF4B (Ser406)] (P<0.01), while minocycline has no influence on mTOR. LC3-II abundance and the LC3-II/I ratio were upregu-lated in the hippocampus of the MCAO stroke rats by the minocycline therapy (P<0.01). p62 was downregulated in the hippocampus from the MCAO stroke rats administrated with minocycline therapy(P<0.01). The levels of SYP and PSD-95 were up-regulated in the brain of the MCAO stroke rats administrated with minocycline therapy. Conclusion: Minocycline prevents cognitive deficits via inhibiting mTOR signaling and enhancing autophagy process, and promoting the expression of pre-and postsynaptic proteins (synaptophysin and PSD-95) in the brain of the MCAO stroke rats. The potential neuroprotective role of minocycline in the process of cerebral ischemia may be related to mitigating is-chemia-induced synapse injury via inhibiting activation of mTOR signaling.

scholarly journals Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1945
Author(s):  
Sheyla González ◽  
Maximilian Halabi ◽  
David Ju ◽  
Matthew Tsai ◽  
Sophie X. Deng
Keyword(s):  
Notch Signaling ◽  
Progenitor Cell ◽  
Basal Layer ◽  
Notch Signaling Pathway ◽  
Basal Cells ◽  
Proliferation Markers ◽  
Limbal Epithelium ◽  
Asymmetric Divisions ◽  
Signaling Activation

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.

scholarly journals Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Guo-dong Zhu ◽  
Jing Yu ◽  
Zheng-yu Sun ◽  
Yan Chen ◽  
Hong-mei Zheng ◽  
...  
Keyword(s):  
Cold Shock ◽  
Mrna Level ◽  
Critical Role ◽  
Inflammatory Signaling ◽  
Heat Stable ◽  
Genome Wide ◽  
Attractive Therapeutic Target ◽  
Heat Stable Protein ◽  
Signaling Activation ◽  
Shock Proteins

AbstractGlioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.

scholarly journals SHH-N non-canonically sustains androgen receptor activity in androgen-independent prostate cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana Trnski ◽  
Maja Sabol ◽  
Sanja Tomić ◽  
Ivan Štefanac ◽  
Milanka Mrčela ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Therapy Resistance ◽  
Androgen Deprivation ◽  
Prostate Cancer Cells ◽  
Androgen Independence ◽  
Androgen Receptor Activity ◽  
Signaling Activation ◽  
Androgen Independent

AbstractProstate cancer is the second most frequent cancer diagnosed in men worldwide. Localized disease can be successfully treated, but advanced cases are more problematic. After initial effectiveness of androgen deprivation therapy, resistance quickly occurs. Therefore, we aimed to investigate the role of Hedgehog-GLI (HH-GLI) signaling in sustaining androgen-independent growth of prostate cancer cells. We found various modes of HH-GLI signaling activation in prostate cancer cells depending on androgen availability. When androgen was not deprived, we found evidence of non-canonical SMO signaling through the SRC kinase. After short-term androgen deprivation canonical HH-GLI signaling was activated, but we found little evidence of canonical HH-GLI signaling activity in androgen-independent prostate cancer cells. We show that in androgen-independent cells the pathway ligand, SHH-N, non-canonically binds to the androgen receptor through its cholesterol modification. Inhibition of this interaction leads to androgen receptor signaling downregulation. This implies that SHH-N activates the androgen receptor and sustains androgen-independence. Targeting this interaction might prove to be a valuable strategy for advanced prostate cancer treatment. Also, other non-canonical aspects of this signaling pathway should be investigated in more detail and considered when developing potential therapies.

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