Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells

Purpose: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer. However, the mechanisms underlying its anti-inflammatory actions have not been extensively elucidated. For this purpose, we explored the inhibitory effects of curcumin on lipopolysaccharide (LPS)-induced TLR4 dependent TRIF signaling pathway in two subtypes of breast cancer cell lines (MCF-7 and MDA-MB-231) in this study. Methods: In this context, the cytotoxicity of curcumin and LPS alone and the combination of curcumin with LPS on these cells was evaluated by WST-1 assay. The expression level of TLR4 and the release of type I interferon (IFN) levels were determined after treatment with curcumin and/or LPS by RT-PCR and ELISA analysis, respectively. Furthermore, the subcellular localization of TLR4 and interferon regulatory factor 3 (IRF3) were detected by immunofluorescence analysis. Results: Curcumin treatment suppressed breast cancer cells viabilities and the activation of TLR4-mediated TRIF signaling pathway by the downregulation of TLR4 and IRF3 expression levels and the inhibition of type I IFN (IFN-alpha/beta) levels induced by LPS. However, curcumin was more efficient in MDA-MB-231 cells than MCF-7 cells owing to its greater inhibitory efficacy in the LPS-enhanced TLR4 signaling pathway. Furthermore, IFN-alpha/beta levels induced by TLR4 and IRF3 were decreased in these cells following curcumin treatment. Conclusions: Consequently, these results demonstrated that the activation of LPS stimulated TLR4/TRIF/IRF3 signaling pathway was mediated by curcumin in breast cancer cells, in vitro. However, more studies are necessary to examine the curcumin's anti-inflammatory activities on TLR4/MyD88/NF-kappa B as well as other signaling pathways downstream of TLRs in breast cancer

The Effect of Treatment on Nitric Oxide and Asymmetric Dimethyl Arginine Levels in Asthma Patients

Giriş ve Amaç: Asimetrik dimetilarjinin (ADMA) ve nitrik oksit (NO), etkilerini birlikte gösterirler, bu moleküller arasındaki denge hava yolu tonusunun ve fonksiyonunun sıkı düzenlenmesine katkıda bulunmaktadır. Çalışmamızda astım tedavisinin serum ADMA, NO, düzeylerine solunum fonksiyon testlerindeki (SFT) değişimlerine, Total IgE, hemogram düzeylerindeki değişiklikleri belirlemeyi amaçlanmıştır. Gereç ve Yöntemler: Çalışmamızda astım tanısı konmuş 30 erkek/kadın hasta (40-60 yaş) ve benzer yaş grubunda 24 erkek/kadın kontrol grubu kullanılmıştır. Çalışmada tedavi öncesi ve sonrası hasta ve kontrol gruplarından serum ADMA, NO, Total IgE düzeylerine ELISA yöntemiyle ve hemogram düzeyleri ise otomatik kan sayım cihazında belirlenmiştir. Bulgular: Astımlı hastaların tedavi öncesi ve tedavi sonrası ADMA ve NO düzeyleri kontrol grubu ile arasında anlamlı fark bulunmuştur (p<0,001). Astımlı hastaların tedavi öncesi ve tedavi sonrası grupların total IgE düzeyleri kontrol grubu ile arasında fark istatistiksel olarak anlamlı bulunmuştur. (p<0,001). Astımlı hastaların tedavi öncesi ve tedavi sonrası grupların %FVC ve % PEF25−75% düzeyleri kontrol grubu ile arasındaki fark, tedavi öncesi grubun %FVC, %PEF25−75% düzeyleri tedavi sonrası grup arasındaki fark istatistiksel olarak anlamlı bulunmuştur (p<0,001). Sonuç: Astım hastalarında tedavinin hastalar üzerindeki etkileri bu çalışma ile belirlenmiş ve elde edilen veriler tedavi sonrası astım hastalarında iyileşme gözlenen parametre düzeylerinin astım hastalarında tedaviye yanıtın takibinin belirlenmesinde kullanılabileceği ortaya konmuştur.Objective: Asymmetric dimethyl arginine (ADMA) and nitric oxide (NO) show their effects together and the balance between these molecules contributes to the tight regulation of airway tone and function. In this study, we aimed to determine the changes in serum ADMA, NO, levels of pulmonary function tests (PFT), total IgE and hemogram levels of asthma treatment. Materials and Methods: In this study, 30 male / female patients (40-60 years) diagnosed with asthma and 24 male / female control groups of similar age group were used. In the study, serum ADMA, NO, Total IgE levels before and after treatment were determined by ELISA method using commercial kit and hemogram levels were determined by automatic blood counting device. Results: There was a significant difference between ADMA and NO levels in asthmatic patients before and after treatment (p<0.001). The difference between total IgE levels of asthmatic patients before and after treatment was found to be statistically significant (p<0.001). The difference between the FVC% and PEF25-75% levels of the pretreatment and post-treatment groups of the asthmatic patients with the control group and the %FVC and %PEF25- 75% of the pretreatment group were found to be statistically significant (p<0.001). Conclusion: The effects of treatment on asthmatic patients were determined in this study and it was shown that the parameter levels improved in asthmatic patients after treatment can be used to determine the response to treatment in asthmatic patients

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62)

The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study

IntroductionElevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia.MethodsThis multi-center, prospective study enrolled patients aged 3–216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels &gt;2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed.ResultsOverall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p &lt; 0.001).DiscussionQuestioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial RegistrationClinicaltrials.gov NCT04120168

Investigation of the effects of quizalofop-P-ethyl on pollen germination of Hyacinthus orientalis L

Quizalofop-p-ethyl (QPE) is a phenoxy herbicide which is used in agriculture to control weeds. The cytotoxic effects of QPE on pollen germination and pollen tube group in Hyacinthus orientalis were investigated and compared to the control. Experiments were carried out different QPE concentrations (0.125M and 0.25M). It was found that in vitro pollen germination and tube growth of H. orientalis was affected by QPE treatments; in particular, the highest QPE concentration caused changes in the morphological features of H. orientalis. The most potent QPE reduced pollen germination by threefold. Morphological abnormalities in the pollen tube were also observed

The Investigation of the Cytotoxic Effects of Some Pesticides on Soybean (Glycine max L.)

In this study, the effects of the fungicide Pomarsol Forte WP 80, the insecticide Arrivo 25 EC and the herbicide The End EC were examined for seed germination percentages, the phases of mitosis and chromosomal abnormalities in soybean (Glycine max L.). Median EC (effective concentration) values were calculated according to relative reduction in root length (T/C%) after treatment for 72 h. Germination percentages of primary soybean roots decreased with increasing pesticide concentrations. Cytological observations showed that the mitotic frequency in root meristematic cells was decreased and that abnormality frequency was also decreased in parallel to the increase in concentrations for all pesticides, except for the 9.6 M concentration of Arrivo 25 EC. The obtained results indicate that these 3 pesticides had the ability to cause a reduction in the seed germination percentage in the number of different phases of mitosis and in the leaf pigment content of soybean (G. max L.)

Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells

Objective: Herein we, for the first time, investigated a potential synergistic effect of nobiletin (NOB) and sorafenib (SOR) on PC-3 prostate cancer and HUVEC control cell lines.Methods: In order to determine the cytotoxic and apoptotic effects of the combination of NOB and SOR, WST-1, Annexin V, and cell cycle analysis were performed. The potential molecular mechanism of apoptotic cell death was assessed by Bax, Bcl-2, CCDN1, Rb1, and CDKN1A gene expression and acridine orange (AO) and DAPI staining.Results: Our results indicated that NOB and SOR combination had a significant inhibitory effect on the viability of PC-3 cells with less toxicity on HUVEC cells than SOR alone (P?<?0.01). NOB and SOR combination significantly caused much more apoptotic cell death and cell cycle arrest at G0/G1 phase by up-regulation of Bax, Rb1, and CDKN1A levels in PC-3 cells (P?<?0.01). Therefore, strong synergistic effects between NOB and SOR were analyzed (CI < 1).Conclusion: NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. Combination strategy is a therapeutic potential to improve efficacy and reduce side-effect of SOR for the treatment of metastatic prostate cancer cells

Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells

Purpose: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer. However, the mechanisms underlying its anti-inflammatory actions have not been extensively elucidated. For this purpose, we explored the inhibitory effects of curcumin on lipopolysaccharide (LPS)-induced TLR4 dependent TRIF signaling pathway in two subtypes of breast cancer cell lines (MCF-7 and MDA-MB-231) in this study. Methods: In this context, the cytotoxicity of curcumin and LPS alone and the combination of curcumin with LPS on these cells was evaluated by WST-1 assay. The expression level of TLR4 and the release of type I interferon (IFN) levels were determined after treatment with curcumin and/or LPS by RT-PCR and ELISA analysis, respectively. Furthermore, the subcellular localization of TLR4 and interferon regulatory factor 3 (IRF3) were detected by immunofluorescence analysis. Results: Curcumin treatment suppressed breast cancer cells viabilities and the activation of TLR4-mediated TRIF signaling pathway by the downregulation of TLR4 and IRF3 expression levels and the inhibition of type I IFN (IFN-alpha/beta) levels induced by LPS. However, curcumin was more efficient in MDA-MB-231 cells than MCF-7 cells owing to its greater inhibitory efficacy in the LPS-enhanced TLR4 signaling pathway. Furthermore, IFN-alpha/beta levels induced by TLR4 and IRF3 were decreased in these cells following curcumin treatment. Conclusions: Consequently, these results demonstrated that the activation of LPS stimulated TLR4/TRIF/IRF3 signaling pathway was mediated by curcumin in breast cancer cells, in vitro. However, more studies are necessary to examine the curcumin's anti-inflammatory activities on TLR4/MyD88/NF-kappa B as well as other signaling pathways downstream of TLRs in breast cancer