Pituitary adenomas are benign brain tumors that cause considerable morbidity and neurological symptoms. SOX9 as a regulatory transcriptional mediator affects normal and tumor cell growth with an ...undefined role in pituitary adenomas pathogenesis. Thus, in the present study, the expression pattern of SOX9 in GH-secreting pituitary tumors and normal pituitary tissues is investigated.
The SOX9 gene expression level was evaluated in 60 pituitary tissues including different types of GH-secreting adenomas and normal pituitary tissues through Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry. The correlations of SOX9 gene and protein expression level with the patient's clinical and pathological features were considered.
The SOX9 over-expression was detected in GH-secreting adenomas tumor tissues compared to normal pituitary tissues which were accompanied by overexpression of SOX9 protein in tumor tissues. The over-expression of SOX9 had a significant impact on GH-secreting adenomas tumor incidence with the odds ratio of 8.4 and the diagnostic value of SOX9 was considerable. The higher level of SOX9 expression was associated with invasive and macro tumors in GH-secreting pituitary adenoma patients. The positive correlation of SOX9 gene and protein level was observed and the tumor size and tumor invasive features were valuable in predicting SOX9 expression level in GH-producing pituitary tumors.
The study provided the first shreds of evidence regarding the expression pattern of SOX9 in the GH- secreting pituitary adenomas at both gene and protein levels which may emphasize the possible involvement of SOX9 as a mediator in pituitary adenoma tumor formation also open up new intrinsic molecular mechanism regarding pituitary adenoma pathogenesis.
•The higher OPN mRNA and protein expression in patients with primary bone cancer.•The serum OPN differentiate the patients from the controls with 100% sensitivity.•The OPN local and circulating level ...was correlated with bone tumor severity.
The development of novel and efficient biomarkers for primary bone cancers is of grave importance.
The expression pattern of osteopontin (OPN) was investigated in the 153 patients with benign (n = 72) and malignant (n = 81) primary bone cancers. Both local and circulating OPN mRNA expression levels and their protein concentration in serum and tumor site were assessed using real-time qRT-PCR, ELISA, and immunohistochemistry techniques, respectively. As a control, 29 healthy individuals were considered. The number of 153 tumor tissue specimens and the 153 paired margins were taken on surgical resection from the patients. 153 blood samples were also drained from all participants, then peripheral blood mononuclear cells (PBMC) and sera were separated.
The mean mRNA expression was significantly higher in all of the cancerous tissues than the paired margins and the PBMC of the patients than the controls. Consistently, the protein concentrations of OPN in serum and tumor tissues were significantly higher in the patients. Furthermore, the malignant cases had significantly elevated the mRNA levels and the protein compared to the benign cases. OPN could potentially differentiate the patients from the controls with 100% sensitivity and specificity in serum. Moreover, OPN could predict some of the malignant cases' clinicopathological features, including metastasis, recurrence, grade, and response to chemotherapy.
In conclusion, OPN might be involved in the pathogenesis of primary bone tumors and can be considered as a potential biomarker to bone cancer diagnosis.
Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease, with unknown etiology. Vitamins, as important micronutrients playing different roles in body, seem to be important in MS ...pathogenesis. In vitro, in vivo and human studies, supports the protective role of some vitamins in MS occurrence or progression. Current study reviews recent insights and reports about the importance of vitamins in MS incidence or progression. In accordance, the importance of all water and fat-soluble vitamins in MS pathogenesis based on observational studies in human population and their role in the function of immune system as well as possible therapeutic opportunities are discussed in depth throughout this review.
•Vitamin D has important roles in MS and can be measured as precursor, or used as treatment.•B6, B9, and B12 deficiency can elevate serum level of homocystenie, which may lead to an inflammatory in the CNS.•Vitamins A, E, and B1 deficiencies are believed to play important roles in MS pathophysiology according to animal models.•Using high doses of vitamin C can worsen MS conditions because of promoting Fenton reaction.•Vitamins D, B9, B12, A, B1, and B3 may improve relapses, degeneration rate, inflammation, and clinical symptoms.
Sirtuin 1 is one of the regulators of cell growth and survival and its inhibition is suggested as a suitable mechanism to overcome breast cancer development. In this study we explored the role of ...miR-211-5p in SIRT1/p53 pathway and its influence on breast cancer cell viability and apoptosis. Cells were transfected with miR-211-5p mimic and inhibitor to modulate cellular miR-211-5p levels in breast cancer cell lines, MDA-MB-231 and MCF-7. Gene expression of miR-211-5p and SIRT1 were measured with real-time PCR. SIRT1 protein level and the acetylation of p53 as well as SIRT1 activity were evaluated by Western blotting and fluorometry, respectively. In order to explore the direct attachment of miR-211-5p to the 3′-UTR of SIRT1 mRNA, luciferase reporter assay was applied. Cell viability in response to miR-211-5p was studied by MTT assay and apoptosis was assessed by annexin V labeling followed by flow cytometry. Results showed that SIRT1 gene and protein expression were inhibited by miR-211-5p and the 3′-UTR of SIRT1 was found to be directly targeted by miR-211-5p. Inhibition of SIRT1 expression resulted in its reduced activity. Up-regulation of miR-211-5p was also followed by a significant decline in the acetylation status of p53 which was associated with remarkable decreased cell viability and induction of apoptosis in breast cancer cells. Antisense oligonucleotide of miR-211-5p acted as its inhibitor and exerted opposite effects both on SIRT1 expression and cell apoptosis. In conclusion, inhibition of SIRT1 by miR-211-5p could effectively reduce breast cancer cell survival and cause cell death and therefore might be considered a seemly mechanism for designing anticancer therapies.
•miR-211 directly binds to the 3′-UTR of SIRT1 and inhibits its expression at mRNA and protein levels.•The reduced activity of SIRT1, caused by miR-211, leads to increased acetylation of p53.•miR-211 reduces cell viability and induces apoptosis in breast cancer cells.
Objective(s): Breast cancer imposes a highest rate of malignancy among the women all around the world. Chitin and its derivatives such as D-glucosamine-carboxymethyl chitin and Di-hydroxy propyl ...chitin have immune-modulating effects and influence on innate and acquisitive immunity which lead to cell activity enhancement. The aim of this study was investigating the effect of D-glucosamine nanoparticle on immune responses such as the changes in cytokines type 1 and 2 level in tumoral mice. Methods: Nanoparticles were synthesized by ionic gelation method and characterized by DLS and SEM methods. Tumors were induced in experimental mice and subsequently treated with nanoparticles. Then, the production of cytokine interferon-γ (IFN-γ) and interleukin 4 (IL-4) were evaluated. Results: The obtained results showed a significant increase in the level of IFN-γ production in the mice group treated with nanoparticles compared to control groups. Additionally, there was a reduction in the level of IL-4 and tumor size in the test group. Conclusions: D-glucosamine nanoparticles can be proposed as a stimulator of the immune system and a promising compound for cancer treatment in the future.
Oncolytic viruses have become of noticeable interest as a novel biological approach for selectively infecting cancer cells and triggering apoptosis in a number of malignant cells. Many researches are ...devoted to characterize more viruses with oncolytic properties.
Evidences on the oncolytic feature of respiratory syncytial virus (RSV) are conflicting; therefore, this study was designed to elucidate the possible role of RSV on the modulation of cell growth and apoptosis in the skin cancer cells.
Plaque assay was used to determine RSV titers. The cytotoxic effect of RSV in A431 (skin carcinoma cell line) was determined using MTT assay. The detection of apoptosis was performed via Annexin-V-FITC staining method and analyzed with flow cytometry.
The results indicated that A431 cell growth was inhibited following infection by RSV in a dose- and time-dependent manner. The most growth inhibitory effect of RSV was occurred at the MOI of 3, and 48 hour after infection. The inhibitory effect of RSV on the cell growth was accompanied by the induction of apoptosis in the skin cancer cells. The percentages of early and late apoptotic cells were increased following exposure to RSV in a concentration- and time-dependent manner.
This study delineated the beneficial role of RSV for growth regulation of skin cancer cells and highlighted the involvement of RSV in the induction of apoptosis in A431 cells. These findings might conduct evidence into the oncolytic properties of RSV in the skin cancer. Further studies are required to indicate intracellular targets for RSV-induced apoptosis in skin cancer cells.
Adipocytes are surrounded by a three-dimensional network of extracellular matrix (ECM) proteins. Aberrant ECM accumulation and remodeling leads to adipose tissue fibrosis. Visfatin is one of the ...adipocytokines that is increased in obesity and is implicated in insulin resistance. The objective of this study was to investigate the effect of visfatin on major components of ECM remodeling. In this study, plasma levels of both endotrophin and visfatin in obese children and adolescents were significantly higher than those in control subjects and they showed a positive correlation with each other. Treatment of 3T3-L1 pre-adipocytes with visfatin caused significant up-regulation of Osteopontin (Opn), Collagen type VI (Col6), matrix metalloproteinases MMP-2 and MMP-9. By using inhibitors of major signaling pathways it was shown that visfatin exerted its effect on Col6a3 gene expression through PI3K, JNK, and NF-кB pathways, while induced Opn gene expression via PI3K, JNK, MAPK/ERK, and NOTCH1. Our conclusion is that, the relationship between visfatin, endotrophin and insulin resistance parameters in obesity as well as increased expression of ECM proteins by visfatin suggests adipose tissue fibrosis as a mechanism for devastating effects of visfatin in obesity.
•The gene expression levels of COX isoforms were significantly higher in patients with severe SARS-CoV-2 infection.•The 15-LOX isoforms gene expression levels were significantly higher in male ...patients with severe SARS-CoV-2 infection.•The serum IL-6, PG-E2, IFN-γ protein levels increased simultaneously in patients with severe SARS-CoV-2 infection.
The role of the lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in maintaining cellular homeostasis and regulating immune responses promoted us in this study to analyze the pattern of changes in 15-lipoxygenase and cyclooxygenase isoforms and their related cytokines in SARS-CoV-2 infection.
15-LOX-1, 15-LOX-2, COX-1 and COX-2 gene expression levels were determined using qRT-PCR in nasopharynx specimens from patients with severe N = 40 and non-severe N = 40 confirmed SARS-CoV-2 infections and healthy controls. Circulating levels of lL-6, lL-10, PGE2, and IFN-γ were measured in patients and healthy controls using ELISA assay. The associations between the measured variables and the patient's clinic-pathological characteristics were assessed for all groups.
The expression level of 15-LOX-1 was elevated significantly in male patients with severe infection; although female patients showed a different expression profile. 15-LOX-2 expression level was considerably increased in male patients with severe infection; while changes in its expression remained inconclusive in female patients. The relationship between 15-LOX expression and the male gender was prominent. Both COX isoforms expression showed elevation in male and female patients that were correlated with disease severity. The simultaneous increase in lL-6, PGE2 and IFN-γ levels also decrease in lL-10 in patients with severe infection indicating the possible regulatory network related to the COX and 15-LOX enzymes in the output of the SARS-CoV-2 infection.
The results of this study determined the pattern of possible changes in key enzymes of prostaglandin and eicosanoids synthesis pathway and their mediators, which can be helpful in mapping the SARS-CoV-2 pathogenicity and pharmaceutical approaches.
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Background
Metabolic plasticity gives cancer cells the ability to shift between signaling pathways to facilitate their growth and survival. This study investigates the role of glucose deprivation in ...the presence and absence of beta-hydroxybutyrate (BHB) in growth, death, oxidative stress and the stemness features of lung cancer cells.
Methods and results
A549 cells were exposed to various glucose conditions, both with and without beta-hydroxybutyrate (BHB), to evaluate their effects on apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) levels using flow cytometry, and the expression of CD133, CD44, SOX-9, and β-Catenin through Quantitative PCR. The activity of superoxide dismutase, glutathione peroxidase, and malondialdehyde was assessed using colorimetric assays. Treatment with therapeutic doses of BHB triggered apoptosis in A549 cells, particularly in cells adapted to glucose deprivation. The elevated ROS levels, combined with reduced levels of SOD and GPx, indicate that oxidative stress contributes to the cell arrest induced by BHB. Notably, BHB treatment under glucose-restricted conditions notably decreased CD133 expression, suggesting a potential inhibition of cell survival through the downregulation of CD133 levels. Additionally, the simultaneous decrease in mitochondrial membrane potential and increase in ROS levels indicate the potential for creating oxidative stress conditions to impede tumor cell growth in such environmental settings.
Conclusion
The induced cell death, oxidative stress and mitochondria impairment beside attenuated levels of cancer stem cell markers following BHB administration emphasize on the distinctive role of metabolic plasticity of cancer cells and propose possible therapeutic approaches to control cancer cell growth through metabolic fuels.
Maternal lipid metabolism status during pregnancy may have pivotal effects on a healthy pregnancy, the progression of labor, and childbirth. Based on evidence, changes in maternal lipid profile and ...metabolism is related to various alterations in fetal metabolic status, fat mass, birth weight and can result in serious maternal and fetal complications. 15-lipoxygenase accounts as a key enzyme in metabolizing polyunsaturated fatty acids that generate various inflammatory lipid metabolites. The possible involvement of 15- lipoxygenase and its metabolites in the inflammatory process, cell proliferation and death, and immune response has been postulated. The indicative role of the 15- lipoxygenase enzymatic pathway in the implantation process, stages of pregnancy, embryogenesis, organogenesis, progression of labor, pregnancy period, and pregnancy-associated complications is remarkable. Accordingly, this study will review the research conducted on the role of 15- lipoxygenase in different reproductive tissues, and its pathological role in pregnancy-related diseases to provide more insight regarding the emerging role of 15-lipoxygenase in normal pregnancy.
•15-LOX exerts a physiological role in pregnancy, embryonic development, fetal growth, and labor progression.•15-LOX induces pro-inflammatory responses and growth restriction in pregnancy-associated complications..•This review summarized the expression profile and molecular mechanisms of 15-LOX in pregnancy and its related disease.•This review provides insights into 15-LOX functional and pathological roles in pregnancy and therapeutic possibilities.•The human, animal, and in-vitro studies evidence are collected with detailed descriptions in this review.
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