Antineoplastic multi-drug chemotherapy to sensitize tumors triggers multi-drug resistance and inhibits efficiency of maintenance treatment inglioblastoma cells.

Combinations of the well-known antineoplastic agents 5-fluorouracil (5-Fu), cisplatin, and paclitaxel are employed to increase radiotherapy/immunotherapy efficacy against persistent and resistant tumors. However, data remains needed on the hormetic, chronic, and long-term side effects of these aggressive combination chemotherapies. Here we investigated cellular and molecular responses associated with these combined agents, and their potential to induce multi-drug resistance against the temozolomide (TMZ) and etoposide (EP) used in glioblastoma maintenance treatment.

Effects of Expression of Matrix Metalloproteinases and Discoidin Domain Receptors in Ligamentum Flavum Fibrosis in Patients with Degenerative Lumbar Canal Stenosis.

Study Design: This is a retrospective cohort study.

Purpose: This study aimed to clarify the role of crosstalk between discoidin domain receptors (DDRs) and matrix metalloproteinases (MMPs) in the ligamentum flavum (LF) fibrosis obtained from patients with degenerative lumbar canal stenosis (DLCS).

Overview Of Literature: The DDRs, DDR1 and DDR2, are cell surface receptors and have an essential role in collagen fiber accumulation in several fibrotic diseases.

MicroRNA-184 attenuates hypoxia and oxidative stress-related injury via suppressing apoptosis, DNA damage and angiogenesis in an in vitro age-related macular degeneration model.

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide, particularly in developed countries. Recently, microRNAs (miRs) have become popular research area to develop new treatment options of AMD. However, interaction between hsa-miR-184 and AMD remain largely unexplored.

Prolonged sub-lethal exposure to galaxolide (HHCB) and tonalide (AHTN) promotes the metastatic potential of glioblastoma tumor spheroids.

Galaxolide and tonalide are well-known polycyclic musks whose intensive use without limitations in numerous cleaning, hygiene, and personal care products has resulted in widespread direct human exposure via absorption, inhalation, and oral ingestion. Latest data shows that long-term, low-dose exposure to toxic chemicals can induce unpredictable harmful effects in a variety of living systems, however, interactions between synthetic musks and brain tumours remain largely unexplored. Glioblastoma (GB) accounts for nearly half of all tumours of the central nervous system and is characterized by very poor prognosis.

Stress-induced miRNAs isolated from wheat have a unique therapeutic potential in ultraviolet-stressed human keratinocyte cells.

Increasing evidence supports the existence of cross-kingdom gene regulation. However, the therapeutic potential of stress-specific plant miRNAs and their role in UV-related pathologies in human tissue remain largely unexplored. The aim of this study was to investigate the therapeutic potential and mechanisms of action of stress-induced miRNA cocktails (SI-WmiRs) from Einkorn wheat (Triticum monococcum L.

The role of melatonin in angio-miR-associated inhibition of tumorigenesis and invasion in human glioblastoma tumour spheroids.

Micro-RNA (miRNA)-based regulation of hypoxia, angiogenesis and tumour growth provides promising targets for effective therapy in malignant glioblastoma multiforme (GBM). Accumulating evidence suggests a potential role of melatonin in miRNA expression in cancer cells. Despite these findings, the melatonin-miRNA interaction in GBM and the effect of this interaction on GBM tumour development and invasion are not clearly understood.

Melatonin prevents blood-retinal barrier breakdown and mitochondrial dysfunction in high glucose and hypoxia-induced in vitro diabetic macular edema model.

Diabetic macular edema (DME) is a leading cause of blindness in diabetic retinopathy. Prolonged hyperglycemia plus hypoxia contributes to DME pathogenesis. Retinal pigmented epithelial cells comprise the outer blood-retinal barrier and are essential for maintaining physiological functioning of the retina.

Different responses of apoptotic, inflammatory and heat shock protein gene expression to a single bout of high-intensity interval exercise between physically active and inactive men.

High mechanical load of muscles may induce muscular apoptosis on the one hand and adaptation to exercise on the other. This study aimed to explore whether changes of circulatory levels of inflammation, apoptosis and heat shock proteins (HSPs) messenger RNA (mRNA) following single bout of high-intensity interval exercise (HIIE) differs between physically active (PA) and inactive (PI) men. Nine PA and 9 PI (peak oxygen consumption: 2.

Naringin Combined with NF-κB Inhibition and Endoplasmic Reticulum Stress Induces Apoptotic Cell Death via Oxidative Stress and the PERK/eIF2α/ATF4/CHOP Axis in HT29 Colon Cancer Cells.

Currently, combination therapy is considered the most effective solution for a selective chemotherapeutic effect in the treatment of colon cancer. This study investigated the death of both colon cancer HT29 cells and healthy vascular smooth muscle TG-Ha-VSMC cells (VSMCs) induced by naringin combined with endoplasmic reticulum (ER) stress and NF-κB inhibition. Naringin combined with tunicamycin and BAY 11-7082 suppressed the proliferation of HT29 cells in a dose-dependent manner and induced particularly apoptotic death without significantly affecting healthy VSMCs according to Annexin V/PI staining and AO/EB staining analyses.

The genotoxic effects of mixture of aluminum, arsenic, cadmium, cobalt, and chromium on the gill tissue of adult zebrafish (, Hamilton 1822).

The aim of this study is to investigate the genotoxic effects of mixtures of five metals on zebrafish at two different concentrations; at the permissible maximum contamination levels in drinking water and irrigation waters. The drinking water limits are as follows: 300 µg/L for Aluminum (Al), 10 µg/L for Arsenic (As), 5 µg/L for Cadmium (Cd), 10 µg/L for Cobalt (Co), and 50 µg/L for Chromium (Cr). The irrigation water limits: 5000 µg/L for Al, 100 µg/L for As, 10 µg/L for Cd, 50 µg/L for Co, and 100 µg/L for Cr.

Chronic exposure of human glioblastoma tumors to low concentrations of a pesticide mixture induced multidrug resistance against chemotherapy agents.

Recent evidence indicates that chronic, low-dose exposure to mixtures of pesticides can cause adverse responses in a variety of cells, tissues and organs, although interactions between pesticides circulating in the blood and cancer cells remain largely unexplored. The aim of this study was to investigate the potential of a mixture of four pesticides to induce multidrug resistance against the chemotherapeutic agents cisplatin, 5-fluorouracil and temozolomide in the human U87 glioblastoma cell line, and to explore the molecular mechanisms underlying this resistance. We found that the repeated administration of the pesticide mixture (containing the insecticides chlorpyrifos-ethyl and deltamethrin, the fungicide metiram, and the herbicide glyphosate) induced a strong drug resistance in U87 cells.

Melatonin regulates oxidative stress and apoptosis in fetal hearts of pinealectomised RUPP rats.

Objective: This study aimed to investigate the effects of melatonin on cardiac oxidative stress and apoptosis in the fetal heart in RUPP rats.

Methods: The fetal heart samples were obtained from melatonin administrated RUPP rats.

Results: Our results indicate that preeclampsia exacerbated by melatonin deficiency triggers hypoxic conditions, both mis/un-folded protein response, oxidative stress-induced DNA damage and apoptosis.

The Dose Dependent Effects of Ruxolitinib on the Invasion and Tumorigenesis in Gliomas Cells via Inhibition of Interferon Gamma-Depended JAK/STAT Signaling Pathway.

Objective: Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids.

The Role of JAK-STAT Signaling Activation in Hypertrophied Ligamentum Flavum.

Background: Although previous studies have reported the expression of JAK1, STAT3, and phosphorylated STAT3 in hypertrophied ligamentum flavum (LF), the role of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway in hypertrophied LF has not been fully elucidated. The aim of this study was to identify the important JAK/STAT gene expression patterns of the 3 main receptors involved in this pathway: interferon (IFN)-γ receptor (IFN-γR), IFN-α receptor (IFNAR), and interleukin (IL)-6 receptor (IL-6R).

Methods: The human LF specimens were obtained from 28 patients who underwent lumbar spine surgery for either degenerative lumbar canal stenosis (DLCS) (n = 28) or lumbar disc herniation (LDH) (n = 20).

Ehlers-Danlos syndrome-related genes and serum strontium, zinc, and lithium levels in generalized joint hypermobility: a case-control study.

: Generalized joint hypermobility (GJH) is a common feature of almost all Ehlers-Danlos syndrome (EDS) types; however, its genetic basis remains unclear. Therefore, it is crucial to distinguish the genetic basis of GJH from other connective tissue disorders, including the different subtypes of EDS. The aim of this study was to determine the blood EDS-related gene expressions and serum element levels in GJH and reveal their predictive characteristics and correlations with the Beighton score.

Inhibition of the Invasion of Human Glioblastoma U87 Cell Line by Ruxolitinib: A Molecular Player of miR-17 and miR-20a Regulating JAK/STAT Pathway.

Aim: To determine the interaction between ruxolitinib, JAK/STAT signalling, and two angio-microRNAs (miRs) to expose potential target molecules in the inhibition of glioblastoma invasion.

Material And Methods: The invasion properties of glioblastoma were analyzed using a cancer cell spheroid invasion assay. Following treatment of 195 nM ruxolitinib, the relative expression levels of miR-17 and miR-20a and genes of IL-6/JAK/STAT3 receptor signaling belonging to the JAK/STAT pathway were measured by qRT-PCR in treated and untreated three-dimensional tumor spheres of U87 cells.

FOLFIRI-Mediated Toxicity in Human Aortic Smooth Muscle Cells and Possible Amelioration with Curcumin and Quercetin.

Systemic chemotherapy-mediated cell toxicity is a major risk factor for cardiovascular disease and atherosclerosis. Life-threatening acute events of the FOLFIRI (irinotecan, folinic acid and 5-fluorouracil) regimen are mainly due to DNA damage induced by antimetabolite and topoisomerase inhibition effects. However, the role of human aortic smooth muscle cells (HaVSMCs) in this process and the mechanisms of oxidative stress, DNA and protein damage and apoptosis have not been investigated.

The Role of Melatonin in Oxidative Stress, DNA Damage, Apoptosis and Angiogenesis in Fetal Eye under Preeclampsia and Melatonin Deficiency Stress.

: The aim of this study was to investigate the possible mechanisms of ocular damage induced by pinealectomy (PNX) and preeclampsia (PE), and to determine the cellular and molecular effects of melatonin treatment on oxidative stress, DNA damage, molecular chaperone responses, induction of apoptosis and angiogenesis in the fetal eye of both PNX and PNX+PE animals. : We analysed therapeutic potential of melatonin on fetal eye damage in PNX and PNX+PE animals using Malondialdehyde (MDA), Random Amplified Polymorphic DNA (RAPD), qRT-PCR and Western blot assays. : Our study presents three preliminary findings: (a) in fetal eye tissues, PNX and PNX+PE significantly induce oxidative damage to both DNA and protein contents, leading to a dramatic increase in caspase-dependent apoptotic signalling in both mitochondrial and death receptor pathways; (b) the same conditions trigger hypoxia biomarkers in addition to significant overexpression of HIF1-α, HIF1-β, MMP9 and VEGF genes in the fetal eye; (c) finally, melatonin regulates not only the expression of genes encoding antioxidant enzymes and increase in DNA damage as well as lipid peroxidation but also limits programmed cell death processes in the fetal eye of PNX and PNX+PE animals .

Midkine silencing enhances the anti-prostate cancer stem cell activity of the flavone apigenin: cooperation on signaling pathways regulated by ERK, p38, PTEN, PARP, and NF-κB.

Prostate cancer (PCa) is the most common cancer in men worldwide. Midkine (MK) is overexpressed in PCa, as well as in tumor-initiating cells termed cancer stem cells (CSCs). Apigenin is a dietary flavone with considerable anti-tumor activities.

Naringin sensitizes human prostate cancer cells to paclitaxel therapy.

Background: The aim of the study was to evaluate whether the use of chemotherapy in combination with naringin, a dietary plant polyphenolic flavonoid, could enhance the therapeutic efficacy of paclitaxel treatment in human prostate cancer (PCa) cells.

Materials And Methods: DU145, PC3, and LNCaP cells were treated with various concentrations of paclitaxel, naringin, and their combinations. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), image-based cytometer, quantitative reverse transcription PCR (RT-qPCR), Western blot, and transwell assay were used to evaluate cell viability, apoptosis and cell cycle, the mRNA expression, protein expression, and cell migration, respectively.

Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway.

Aims: To examine the functions of growth factor midkine (MK) and a flavonoid quercetin on survival, apoptosis and migration of prostate cancer (PCa) stem cells (CSCs).

Main Methods: CD44/CD133 and CD44 stem cells were isolated from PC3 and LNCaP cells, respectively by magnetic-activated cell sorting system. 3D cell culture was used to evaluate the ability of quercetin, MK siRNA, and the combination of both to inhibit spheroid formation, apoptosis and cell cycle arrest.

Melatonin attenuates caspase-dependent apoptosis in the thoracic aorta by regulating element balance and oxidative stress in pinealectomised rats.

The aim of this study was to explain the possible mechanisms by which melatonin deficiency results in cardiovascular injury and to investigate the effects of melatonin administration on important signalling pathways and element equilibrium in the thoracic aorta (TA). For this purpose, we analysed the cellular and molecular effects of melatonin deficiency or administration on oxidative stress, DNA damage, molecular chaperone response, and apoptosis induction in TA tissues of pinealectomised rats using ELISA, RAPD, qRT-PCR, and Western blot assays. The results showed that melatonin deficiency led to an imbalance in essential element levels, unfolded or misfolded proteins, increased lipid peroxidation, and selectively induced caspase-dependent apoptosis in TA tissues without significantly affecting the Bcl-2/BAX ratio (2.

Nonoccupational Exposure of Agricultural Area Residents to Pesticides: Pesticide Accumulation and Evaluation of Genotoxicity.

Although many studies related the toxic effects of pesticides on agricultural workers, little research has been done about agricultural area residents. The purpose of this work was to monitor the presence of pesticides, as well as their genotoxic and cytotoxic potential, in humans with blood samples collected from control and intensive agricultural areas in the Thrace region. Pesticide accumulations were determined by LC-MS/MS.