Analysis of Human microRNA Expression Profiling During Diquat-Induced Renal Proximal Tubular Epithelial Cell Injury.

Background: We established a diquat-induced human kidney-2 cells (HK-2 cells) apoptosis model in this study to identify differentially expressed microRNAs (miRNAs) and signaling pathways involved in diquat poisoning via gene sequencing and bioinformatics analysis and explored the related therapeutic benefits.

Methods: The effects of diquat on the viability and apoptosis of HK-2 cells were explored using the CCK-8 and Annexin V-FITC/PI double staining methods. Total RNAs were extracted using the TRizol method and detected by Illumina HiSeq 2500.

A local translation program regulates centriole amplification in the airway epithelium.

Biogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and likely to be dependent on the cellular context. Here we identify Trinucleotide repeat containing-6a (Tnrc6a), a component of the miRNA pathway, distinctively localized to apical granules of differentiating airway multiciliated cells (MCCs) adjacent to centrioles.

Analysis of microRNA expression profiling during paraquat-induced injury of murine lung alveolar epithelial cells.

Paraquat (PQ) as a non-selective heterocyclic herbicide, has been applied worldwide for over a few decades. But PQ is very harmful to humans and rodents. The lung is the main target organ of PQ poisoning.

Role of the MAPK pathway in human lung epithelial-like A549 cells apoptosis induced by paraquat.

This study aims to investigate the value of mitogen-activated protein kinases (MAPKs) for paraquat (PQ)-induced apoptosis in human lung epithelial-like A549 cells and the specific mechanism. A549 cell apoptosis were induced by PQ. These cells were divided into six groups: control group (cells were cultured in RPMI-1640 medium); SP600125 group (cells were preconditioned with SP600125); SB203580 group (cells were preconditioned with SB203580); PQ group (cells were treated with PQ); SP600125+PQ group (cells were preconditioned with SP600125 following PQ); SB203580+PQ group (cells were preconditioned with SB203580 following PQ).

Effect of endoplasmic reticulum calcium on paraquat‑induced apoptosis of human lung type II alveolar epithelial A549 cells.

The present study aimed to explore the role of endoplasmic reticulum calcium (ER Ca2+) in the apoptosis of human lung type II alveolar epithelial A549 cells induced by paraquat (PQ) in vitro. PQ significantly elevated the intracellular Ca2+ concentration. Treatment with the Ca2+‑ATPase inhibitor thapsigargin significantly increased PQ‑induced cytotoxicity, elevated the intracellular level of Ca2+, and increased the apoptosis rate, the protein expression of glucose‑regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), and the activities of caspase‑7 and caspase‑12 in PQ‑treated cells.

LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells.

Background: Acquired resistance to sorafenib greatly limits its therapeutic efficiency in the treatment of hepatocellular carcinoma (HCC). Increasing evidence indicates that long noncoding RNAs (lncRNAs) play important roles in the resistance to anti-cancer drugs. The present study aims to explore the involvement of lncRNA SNHG1 (small nucleolar RNA host gene 1) in sorafenib resistance and how SNHG1 is associated with overexpressed microRNA-21 (miR-21) and the activated Akt pathway, which have been demonstrated to mediate this resistance in HCC cells.

MnTMPyP inhibits paraquat-induced pulmonary epithelial-like cell injury by inhibiting oxidative stress.

Objective: To investigate the protective effect and underlying mechanism of the superoxide dismutase mimic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), on paraquat (PQ)-induced lung alveolar epithelial-like cell injury.

Methods: Lung alveolar epithelial-like cells (A549) were pretreated with 10 μM MnTMPyP for 1.5 hr and then cultured with or without PQ (750 uM) for 24 hr.

Involvement of PINK1/Parkin-mediated mitophagy in paraquat- induced apoptosis in human lung epithelial-like A549 cells.

Paraquat (PQ) is one of the most popular herbicides and has been widely used all over the world over the past several decades. However, PQ exposure can cause multiple organ failure, especially acute lung injury in humans as well as in rodent animals. Mitochondrial dysfunction plays a crucial role in PQ-induced lung cell damage.

[Correlation between model for end-stage liver disease score and prognosis in mushroom poisoning patients: a multicenter clinical study].

Objective: To find out the clinical indicators related to prognosis in patients with acute mushroom poisoning, and approach its correlation with prognosis.

Methods: Clinical data of patients with mushroom poisoning admitted to the First Hospital of China Medical University, the Ninth People's Hospital of Shenyang, Xiuyan Central People's Hospital, and Fushun Central Hospital from August 2015 to August 2017 were retrospectively analyzed. The biochemical indicators within 24 hours after admission, sequential organ failure assessment (SOFA) score, model for end-stage liver disease (MELD) score, whether plasmapheresis (PE) was carried out or not and 28-day prognosis of patients were collected.

MicroRNA-21-Regulated Activation of the Akt Pathway Participates in the Protective Effects of HS against Liver Ischemia-Reperfusion Injury.

Maintaining a certain level of hydrogen sulfide (HS) in ischemia-reperfusion (I/R) is essential for limiting injury to the liver. Exogenous HS exerts protective effects against this injury, but the mechanisms remain unclear. Liver injury was induced in Wistar rats undergoing hepatic I/R for 30 min, followed by a 3-h reperfusion.

Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway.

Paraquat (PQ), as one of the most widely used herbicides in the world, can cause severe lung damage in humans and animals. This study investigated the underlying molecular mechanism of PQ-induced lung cell damage and the protective role of salubrinal. Human lung epithelial-like A549 cells were treated with PQ for 24h and were pre-incubated with salubrinal for 2h, followed by 500μM of PQ treatment.

Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice.

This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydrate at 0, 1, 2, 4, 8, 12, 24 and 48 h after treatment administration.

Neuropilin-1 regulated by miR-320 contributes to the growth and metastasis of cholangiocarcinoma cells.

Background & Aims: Neuropilin-1 (NRP-1) activates signalling pathways as multifunctional co-receptors in cancer cells. However, its role and how it is regulated by miRNAs in cholangiocarcinoma (CCA) have not yet been investigated.

Methods: The expression of NRP-1, miR-320 and key molecules involved in cell proliferation, migration and related signalling pathways were detected by immunohistochemistry, immunoblotting and qRT-PCR.

Associating liver partition and portal vein ligation for staged hepatectomy versus conventional staged hepatectomy: a meta-analysis.

Introduction: Controversies persist between associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and conventional staged hepatectomy. This meta-analysis aims to compare completion, regeneration capacity, and surgical outcomes between the two strategies.

Evidence Acquisition: We systematically searched PubMed, EMBASE, Cochrane Library, Medline.

An artificial lncRNA targeting multiple miRNAs overcomes sorafenib resistance in hepatocellular carcinoma cells.

Sorafenib resistance remains a major obstacle for the effective treatment of hepatocellular carcinoma (HCC), and a number of miRNAs contribute to this resistance. However, the regulatory networks of miRNAs are very complex, thus inhibiting a single miRNA may sequentially activate other compensatory pathways. In the present study, we generated an artificial long non-coding RNA (AlncRNA), which simultaneously targets multiple miRNAs including miR-21, miR-153, miR-216a, miR-217, miR-494 and miR-10a-5p.

Neuropilin-1 is associated with clinicopathology of gastric cancer and contributes to cell proliferation and migration as multifunctional co-receptors.

Background: Neuropilin-1 (NRP-1) is a transmembrane glycoprotein participating in the growth and metastasis of cancer cells as multifunctional co-receptors by interacting with the signaling pathways. However, its role in gastric cancer has not yet been clarified. This study aims to investigate whether NRP-1 expression is associated with the clinicopathology of gastric cancer, and involved in the growth and metastasis of gastric cancer cells.

MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway.

Sorafenib resistance remains a major obstacle for the effective treatments of hepatocellular carcinoma (HCC). Recent studies indicate that activated Akt contributes to the acquired resistance to sorafenib, and miR-21 dysregulates phosphatase and tensin homolog (PTEN), which inhibits Akt activation. Sorafenib-resistant HCC cells were shown to be refractory to sorafenib-induced growth inhibition and apoptosis.

2ME2 inhibits the activated hypoxia-inducible pathways by cabozantinib and enhances its efficacy against medullary thyroid carcinoma.

Cabozantinib is a multi-targeted tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptor (VEGFR)-2, MET (c-Met, also called hepatocyte growth factor (HGF) receptor), and other receptor tyrosine kinases. Cabozantinib has recently been approved for treating advanced medullary thyroid carcinoma (MTC), but its long-term benefit remains uncertain and dose-dependent adverse events are very common. The present study has demonstrated that 2-methoxyestradiol (2ME2), an inhibitor of hypoxia-inducible factors (HIFs) and a promising anticancer agent under investigation in clinical trials, strengthens anticancer activities of cabozantinib against MTC cells in vitro and in vivo.

Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway.

Overexpression of histone deacetylases (HDACs) is associated with higher metastatic rates and a poor prognosis in gastric cancer. However, the underlying mechanisms involved remain unclear. The present study aimed to investigate the molecular pathways that are involved in HDAC1-mediated metastatic activities in gastric cancer cells.

Toll-like receptor 4 implicated in acute lung injury induced by paraquat poisoning in mice.

Objective: To investigate the possible relationship and mechanism of Toll-like receptor 4 (TLR4) and acute lung injury induced by paraquat (PQ) poisoning.

Methods: Male wild type mice and male TLR4-knockout mice were used in this study. After paraquat treatment for 24 hours, mice were euthanized and pathology, TLR4 expression and pro-inflammatory cytokines were evaluated.

2-Methoxyestradiol synergizes with sorafenib to suppress hepatocellular carcinoma by simultaneously dysregulating hypoxia-inducible factor-1 and -2.

Sorafenib is the approved systemic drug of choice for advanced hepatocellular carcinoma (HCC), but has demonstrated limited benefits because of drug resistance. 2-Methoxyestradiol (2ME2) has been shown to be a promising anticancer drug against various types of cancers and acts by dysregulating hypoxia-inducible factor (HIF)-1. Hypoxic cancer cells are extremely resistant to therapies since they elicit strong survival ability due to the cellular adaptive response to hypoxia, which is controlled by HIF-1 and HIF-2.

Enhanced autophagy by everolimus contributes to the antirestenotic mechanisms in vascular smooth muscle cells.

Objective: The present study aims to investigate the underlying mechanisms accounting for the activities of everolimus to inhibit the growth of vascular smooth muscle cells (VSMCs), which contributes to restenosis.

Methods: Primary VSMCs were cultured in media containing smooth muscle growth supplements and incubated with testing agents. Cell proliferation, cell cycle distribution, apoptosis and autophagy, and the key molecules involved, were examined.

A novel fluid resuscitation protocol: provide more protection on acute kidney injury during septic shock in rats.

Objective: To investigate the therapeutic effects of a novel fluid resuscitation protocol (early fluid resuscitation plus 2% hydrogen inhalation) on acute kidney injury during septic shock induced by lipopolysaccharide in rats.

Methods: Sixty male Wistar rats were randomly divided into four groups (n = 15 per group): control group (C), septic shock group (S), septic shock with early fluid resuscitation group (R), and septic shock with early fluid resuscitation plus 2% hydrogen inhalation group (R+R+H2). The rats were ventilated, and a 2% hydrogen mixture was used in Group R+H2.