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1.
Ewa Langner Witold Jeleniewicz Waldemar A. Turski Tomasz Plech 《Pharmacological reports : PR》2019,71(2):189-193
Background
Origin, synthesis and activity of quinaldic acid (QA), proposed derivative of kynurenic acid, have been poorly studied to date. Previously, we have demonstrated the antiproliferative effect of QA in a colon cancer model in vitro. The goal of present study was to verify QA activity to modify the expression of p53 tumor suppressor in colon cancer cells, and to relate it to its cancer cell growth inhibiting activity in vitro.Methods
LS180 colon cancer cells possessing the wild type form of p53 were used in the study. Real-time PCR and immunobloting techniques were used to test the expression of p53 at gene and protein level, respectively. Next, immunocytochemistry was used to visualize the localization of p53 protein within the cells. Furthermore, the antiproliferative activity of QA was retested in cells with siRNA silenced P53 gene.Results
The activity of QA to modify both the expression and phosphorylation of p53 protein as well as the level of P53 gene is shown. Concomitantly, the nuclear and cytoplasmic localization of phospho-p53 protein upon QA treatment is also presented. Moreover, reduced activity of QA in colon cancer cells with silenced p53 expression is observed.Conclusion
QA affects the expression of p53 tumor suppressor, both at gene and protein level. The prominent contribution of p53 to the antiproliferative effect of QA in LS180 colon cancer cells can be suggested. 相似文献2.
Aleksandra Sałagacka-Kubiak Marta Żebrowska-Nawrocka Agnieszka Jeleń Marek Mirowski Ewa Balcerczak 《Pharmacological reports : PR》2019,71(2):272-275
Background
CYP2C19 isoenzyme of cytochrome P450 in the liver catabolises proton pump inhibitors, one of the therapeutics utilized in Helicobacter pylori eradication therapy, and in this way could influence the eradication effectiveness. The isoensyme contributes also to metabolism of endogenous substances, which derivatives are involved in the pathogenesis of peptic ulceration. CYP2C19*2 polymorphism (rs4244285) changing the CYP2C19 function could be relevant in the predisposition to peptic ulcer disease.Methods
CYP2C19*2 polymorphism in 197 peptic ulcer patients and 107 healthy subjects of Polish origin by PCR-RFLP method was investigated.Results
There were no statistically significant differences in genotypes and alleles frequencies for investigated polymorphism between peptic ulcer patients and healthy individuals. No associations between frequencies of particular CYP2C19 genotypes and alleles and the presence of H. pylori infection in peptic ulcer patients were stated. However, significant association between CYP2C19*2 and gender in H. pylori-infected but not -uninfected peptic ulcer individuals was found.Conclusions
Investigated polymorphism is not a risk factor for peptic ulcer in Polish population. Obtained results could suggested there is some interaction between gender, CYP2C19*2 polymorphism, and pathogenesis of H. pylori infection development. However, this hypothesis should be verified in the further studies. 相似文献3.
Refaat I. ElFayoumi Magda M. Hagras Adel Abozenadaha Mamdouh Gari Ibrahim Abosoudah Thoraia Shinawi Talaat Mirza Waleed Bawazir 《Pharmacological reports : PR》2019,71(1):90-95
Background
Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL.Methods
Three single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs 3213619 T129C, rs 2032582 G2677T and rs1045642 C3435T) were analysed in 70 Saudi children with ALL and 60 control subjects. Participants were treated according to the ALL 2000 study protocol. Toxicities were assessed and associations with genotypes were evaluated according to Common Toxicity Criteria (NCI-CTC).Results
Significant associations were observed among carriers and the mutated genotype C3435T (ABCB1), which had an incidence of infection (p?=?0.05). Although no correlations were found between liver toxicity and glucose abnormalities for patients carrying ABCB1 SNPs, risk factors for liver toxicity were elevated by a factor of three for patients carrying the SNP G2677T, OR 3.00 (1.034–8.702). The risk factor of glucose abnormality toxicity for the patients carring T129C were increased three times OR 3.06 (0.486–19.198).Conclusions
In terms of infection incidence, polymorphism C3435T may contribute to potential life-threatening infections during paediatric ALL therapy, through glucocorticoid usage. 相似文献4.
Justyna Walenciak Krystyna Wyka Szymon Janczar Wojciech Młynarski Beata Zalewska-Szewczyk 《Pharmacological reports : PR》2019,71(2):311-318
Background
L-asparaginase (L-asp) remains one of the key components of acute lymphoblastic leukemia therapy. Immune reactions to the drug are associated with its diminished activity. The aim of the study was to determine the level of IgM, IgG and IgE-class anti-L-asp antibodies during the induction and reinduction phases of acute lymphoblastic leukemia therapy and their influence on L-asp activity.Methods
The study group comprised 65 patients treated for acute lymphoblastic leukemia in one pediatric oncology center. L-asp antibodies were assessed using ELISA at the end of the induction and reinduction phases. L-asp activity was assessed prior to each drug administration by colorimetry.Results
At the end of the first exposure to L-asp antibodies were detected in 35 patients (54%). In the reinduction phase of the treatment anti-L-asp antibodies were found in 38/55 patients (69%). In the induction phase patients with inadequate L-asp activity had higher IgM concentrations (median 5.88 versus 2.81?μg/mL, p?=?0.03). In the reinduction phase IgG and IgM levels correlated inversely with L-asp activity. Patients with L-asp allergy had higher levels of IgG (median 61.6 versus 18.36 μg/mL, p?=?0.01), whereas higher IgE levels were noted in the group of patients with inadequate drug activity (median 0.91 versus 0.64 μg/mL, p?=?0.03).Conclusions
Subsequent exposure to L-asp in the treatment of acute lymphoblastic leukemia was associated with the increase of anti-L-asp antibodies in all studied classes. However, the changes observed in specific classes of antibodies were not distinctive for L-asp hypersensitivity or inactivation, suggesting that the mechanism is more complex. 相似文献5.
Yueh-Lun Lee Ling-Heng Hsu Yueh-Hsiung Kuo Chen-Chen Lee 《Pharmacological reports : PR》2019,71(2):194-200
Background
Caffeic amides are derivatives of caffeic acid, which have antioxidant and anti-inflammatory properties, and high in vivo stability. The therapeutic effect of caffeic amides on allergic diseases, and especially on the maturation of bone marrow-derived dendritic cells (BM-DCs), remains unclear. In this study, we investigated the therapeutic potential of caffeic amides on allergic diseases by evaluating the maturation of DCs and evaluated their potential in inducing the differentiation of TH2 cells.Methods
BM-DCs isolated from BALB/c mice were treated with different caffeic amide derivatives for 48?h and the expression of surface markers was analyzed by flow cytometry. The differentiation of CD4+ T cells was detected by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay and cytokine production was analyzed by ELISA.Results
Our results showed that among the six caffeic amides tested herein, only 36?M significantly inhibited the antigen-induced maturation of DCs associated with the expression of CD80, CD86, and major histocompatibility complex II (VC ovalbumin (OVA)+ thymic stromal lymphopoietin (TSLP) vs. 36?M OVA?+?TSLP). Additionally, the isolation and co-culture of antigen-specific CD4+ T cells with 36?M-treated BM-DCs suppressed the antigen-specific differentiation of TH2 cells.Conclusion
Among the six caffeic amides tested herein, 36?M (N-octyl caffeamide) might possess therapeutic potential for allergic diseases. 相似文献6.
Fatemeh Delrobaei Iman Fatemi Ali Shamsizadeh Mohammad Allahtavakoli 《Pharmacological reports : PR》2019,71(1):133-138
Background
Menopause is associated with increased oxidative stress and memory impairment. Based on the antioxidant property of ascorbic acid (AA), It’s effect on cognitive function, the serum level of the brain-derived neurotrophic factor (BDNF) and the activity of antioxidant enzymes within the brain in ovariectomized (OVX) mice was investigated.Methods
AA (100, 300 and 500?mg/kg), was orally administrated per day in OVX mice for 30 days. Tactile learning and working memory were evaluated by the novel object recognition task and T-maze continuous alternation task, respectively. The levels of serum BDNF were measured and animals’ brains were analyzed for the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity.Results
AA prevented from the deleterious effects of ovariectomy on learning memory (300 and 500?mg/kg) and working memory (100 and 500?mg/kg). The serum BDNF level was also increased in OVX animals treated with AA (100 and 500?mg/kg). Furthermore, AA (500?mg/kg) increased the SOD and GPx activity in the brain of OVX animals.Conclusions
Collectively, the results of the present study suggest that AA might be an appropriate choice in loss or reduction of estradiol for the amelioration of cognitive impairment. 相似文献7.
Background
Elevated prolactin levels are associated with increased cardiometabolic risk. No previous study has compared the effect of hypolipidemic therapy on plasma levels of lipids and other cardiometabolic risk factors in patients with and without hyperprolactinemia.Methods
The study included three age-, weight-, blood pressure- and lipid-matched groups of premenopausal women: 18 women with untreated hyperprolactinemia, 19 women with bromocriptine-treated hyperprolactinemia and 20 drug-naïve women with normal prolactin levels. Because of concomitant atherogenic dyslipidemia, all patients were treated with fenofibrate (200?mg daily) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were assessed at baseline and at the end of hypolipidemic treatment.Results
Unlike similar baseline lipid levels, plasma concentrations of the remaining investigated cardiometabolic risk factors were higher in women with elevated prolactin levels than in patients with normal prolactin levels. The impact of fenofibrate on total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels, as well as on uric acid, hsCRP, homocysteine, and fibrinogen was less pronounced in women with untreated hyperprolactinemia than in women with bromocriptine-treated hyperprolactinemia and drug-naïve women with normal prolactin levels.Conclusions
The results of our study indicate that cardiometabolic effects of fenofibrate depend on plasma prolactin levels. 相似文献8.
Yong Su Qingqing Chen Keke Ma Yinghui Ju Tianjiao Ji Zhongyuan Wang Weizu Li Weiping Li 《Pharmacological reports : PR》2019,71(2):319-329
Background
The increased in?ux of free fatty acids (FFAs) into the kidney is a risk factor for diabetes nephropathy (DN). In the present study we investigated the effects of astragaloside IV (AS-IV) on FFA-induced lipid accumulation, oxidative stress, and activation of TGF-β1 signaling in human glomerular mesangial cells (HMCs).Methods
A DN model was induced in Sprague Dawley rats by the administration of a high-fat diet and streptozocin, and HMCs were stimulated with palmitate. Lipid accumulation and FFA uptake were detected using Oil Red O and BODIPY? FL C16 staining, respectively. The expression levels of TGF-β1, p-Smad2/3, FN, Col4?A1, NOX4, p22phox, and CD36 were evaluated by western blotting or immunofluorescence/immunohistochemistry. The level of reactive oxygen species (ROS) was detected using 2′,7′-dichlorofluorescein diacetate and dihydroethidium.Results
Exposure to palmitate induced marked lipid accumulation in HMCs, whereas co-treatment with AS-IV significantly attenuated this phenomenon. Moreover, AS-IV suppressed palmitate-induced expression of TGF-β1, p-Smad2/3, FN, Col4?A1, NOX4, and p22phox, in addition to ROS production. Notably, AS-IV reduced the palmitate-induced expression of CD36 in HMCs and DN rats. Treatment of HMCs with the CD36 inhibitor, sulfo-N-succinimidyl oleate (SSO), significantly attenuated FFA uptake, oxidative stress, and fibrosis. Nevertheless, the combined use of SSO and AS-IV did not enhance the efficacy.Conclusion
AS-IV inhibited palmitate-induced HMCs oxidative stress and fibrosis via the downregulation of CD36 expression, mediating FFA uptake and lipid accumulation. 相似文献9.
Marek Zadrozniak Marcin Szymanski Jarogniew J. Luszczki 《Pharmacological reports : PR》2019,71(2):351-356
Background
Drug-induced ototoxicity is still a main clinical problem in otolaryngology. It is widely known that aminoglycoside antibiotics combined with loop diuretics significantly contribute to permanent ototoxicity. The aim of this study was to find out whether ascorbic acid (vitamin C) is able to reverse or alleviate ototoxicity evoked by systemic (ip) administration of combination of amikacin and furosemide in experimental male albino Swiss mice.Methods
Ototoxic combination of amikacin and furosemide was isobolographically evaluated based on the hearing threshold decreasing doses by 20% and 50% (TDD20 and TDD50), respectively. Linear regression analysis was used to determine the TDD20 and TDD50 values for amikacin, furosemide, vitamin C administered alone and in combination (at the fixed-ratio of 1:1).Results
Vitamin C (in a dose of 500?mg/kg, ip) alleviated the impairment in hearing threshold evoked by combined ip administration of amikacin and furosemide (at the fixed-ratio of 1:1) in mice by reducing TDD50 values from 49.82 to 21.56 (p?<? 0.01). In contrast, vitamin C (500?mg/kg, ip) had no significant effect on TDD20 values for the combination of amikacin and furosemide at the fixed-ratio of 1:1.Conclusions
Vitamin C administered together with ototoxic drug combination of amikacin and furosemide reduced ototoxicity evoked by this two-drug combination in the experimental mice. 相似文献10.
Rodopi Stamatiou Efrosini Paraskeva Anna Vasilaki Apostolia Hatziefthimiou 《Pharmacological reports : PR》2019,71(2):225-232
Background
Muscarinic receptor antagonists are a usual treatment for chronic airway diseases, with increased bronchoconstriction, like asthma and chronic obstructive pulmonary disease. These diseases are usually accompanied by airway remodeling, involving airway smooth muscle cell (ASMC) proliferation. The purpose of this study was to examine the effect of the muscarinic receptor modulator gallamine on rabbit tracheal ASMC proliferation.Methods
ASMCs were incubated with gallamine (1?nM–10?mM), atropine (1 fM–10?mM), and/or acetylcholine (1?nM–1?mM), in the presence or absence of FBS (1% or 10%). Cell proliferation was estimated by incorporation of radioactive thymidine, the Cell Titer AQueous One Solution method and cell number counting after Trypan blue exclusion. The mechanisms mediating cell proliferation were studied using the PI3K and MAPK inhibitors LY294002 (20?μM) and PD98059 (100?μM), respectively. Cell phenotype was studied by indirect immunofluorescence for α-actin, Myosin Heavy Chain and desmin.Results
ASMC incubation with the muscarinic receptor allosteric modulator gallamine or the muscarinic receptor antagonist atropine increased methyl-[3H]thymidine incorporation and cell number in a dose-dependent manner. ASMC proliferation was mediated via PI3K and MAPK activation and was transient. Gallamine antagonized the mitogenic effect of 1% FBS. Furthermore, gallamine had a similar effect on contractile ASMCs, without synergizing with or affecting acetylcholine induced proliferation, or altering the percentage of ASMCs expressing contractile phenotype marker proteins.Conclusions
Gallamine, in the absence of any agonist, has a transient mitogenic effect on ASMCs, regardless of the cell phenotype, mediated by the PI3K and the MAPK signaling pathways. 相似文献11.
Reza Fartootzadeh Fatemeh Azizi Hojjatallah Alaei Parham Reisi 《Pharmacological reports : PR》2019,71(2):361-366
Background
The nucleus accumbens core (NAcc) expresses both orexin and nicotinic acetylcholine receptors (nAChRs). Orexin is among important neurotransmitters, which regulates addictive properties of drugs of abuse including nicotine. The role of orexin-2 receptor (OX2R) in the regulation of NAcc neural activity in response to nicotine has not yet been studied. Hence, in this study, we examined whether the OX2R antagonist (TCS-OX2-29) can adjust the effects of nicotine on electrical activity of NAcc neurons, in urethane-anesthetized rats, using the single unit recording.Methods
Neuronal firing of NAcc was recorded for 15?min, then TCS-OX2-29 (OX2R-antagonist; 1, 3 and 10?ng/rat) or DMSO were microinjected into NAcc, just 5?min before subcutaneous (sc) administration of nicotine (0.5?mg/kg) or saline. The spontaneous firing activity was recorded for 70?min, after nicotine injection.Results
The results demonstrated that nicotine significantly excites the NAcc neurons and interestingly, the administration of TCS-OX2-29 (3 and 10?ng/rat) into the NAcc, inhibited nicotine-induced increases of NAcc neuronal responses. Furthermore, administration of TCS-OX2-29 (10?ng/rat), just 5?min before sc administration of saline instead of nicotine, did not significantly alter the neuronal responses, compared to the saline-control group.Conclusion
Our results showed that, although OX2R blockade alone did not affect neuronal activity in the NAcc, it was able to prevent the exciting effects of nicotine on NAcc neuronal activity. Therefore, we proposed that orexin has a potential modulator effect, in response to nicotine. 相似文献12.
Background
Due to anti-inflammatory and anti-thrombotic functions, statins and antiplatelets are widely used for patients with cardiovascular-related or coronary artery diseases. Patients with systemic or complex diseases are commonly prescribed multiple targeted medications; thus, a proper combination of two or more drugs for beneficial efficacy is considered in clinical therapy. Recent studies have suggested that combinational therapy with statins and other medications accelerates their single effect to suppress inflammatory responses. However, the therapeutic efficacy and underlying mechanism of combination treatment with rosuvastatin and cilostazol have been poorly studied.Methods
Mice were administered rosuvastatin alone, cilostazol alone or rosuvastatin and cilostazol in combination, and then injected with LPS or TNF to induce acute inflammation. The serum TNF level, macrophage infiltration of the lesioned aortas and mice mortality were observed in the acute inflammation model. The phosphorylation of MAPK was analyzed in TNF-stimulated HeLa cells.Results
Compared to the treatment with cilostazol alone, the combination treatment with rosuvastatin and cilostazol significantly reduced not only the levels of TNF in the sera but also macrophage infiltration in aortic lesions. In addition, the combination therapy decreased TNF-mediated phosphorylation of the MAPK signaling pathway and improved the survival rate in the TNF-driven inflammatory mice model.Conclusion
Rosuvastatin combined with cilostazol therapy can greatly improve the anti-inflammatory effect of monotherapies, resulting in reduced mortality of mice; thus, we propose the potential of use of this combination therapy as anti-TNF agent. 相似文献13.
Jan Detka Joanna Ślusarczyk Anna Kurek Mateusz Kucharczyk Tomasz Adamus Paweł Konieczny Marta Kubera Agnieszka Basta-Kaim Władysław Lasoń Bogusława Budziszewska 《Pharmacological reports : PR》2019,71(2):338-346
Background
In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.Methods
Adult male PS rats were subjected to acute stress and/or received orally glucose. Levels of hormones and their receptors were assayed with ELISA method. In vitro studies were performed on mHypoA-2/12?hypothalamic cell line, stably transfected with CRH promoter coupled with luciferase.Results
PS has reduced GLP-1 and GLP-1R levels, attenuated glucose-induced increase in insulin concentration and increased the amount of phosphorylated IR in the hypothalamus of animals subjected to additional stress stimuli, and also decreased the GLP-1R level in the hippocampus. In vitro studies demonstrated that insulin is capable of increasing CRH promoter activity in the condition of stimulation of the cAMP/PKA pathway in the applied cellular model.Conclusion
Prenatal stress may act as a preconditioning factor, affecting the concentrations of hormones such as insulin and GLP-1 in the hypothalamus in response to adverse stimuli. The decreased GLP-1R level in the hippocampus could be linked with the disturbances in neuronal plasticity. 相似文献14.
Background
PGs are involved in cellular communication and cancer biology. The role of CS in melanoma and fibrosarcoma cell lines was explored by using chondroitin AC lyase (PsPL8A).Methods
The proliferation of mouse fibroblast L929, human melanoma (SK-Mel 28) and fibrosarcoma (HT-1080) cell lines after treatment with chondroitin AC lyase (PsPL8A) was studied by MTT assay. The mode of cell death was studied by Annexin-V FITC using flow cytometry and fluorescence microscopy. The alteration in mitochondrial cell potential was studied by JC-1 dye using fluorescence microscopy and flow cytometry.Results
Treatment of L929 cells with PsPL8A imparts no cytotoxicity and showed no alteration in proliferation with nearly 95–98% cell viability. An overall 58% and 59% inhibition of SK-Mel 28 and HT-1080 cell proliferation was observed with 1.3 μM of PsPL8A after 24?h of incubation. The PsPL8A (1.3 μM) treated SK-Mel 28 and HT-1080 cells showed significant green fluorescence with annexin-V FITC under fluorescence microscopy and 56.6% and 35.5% apoptosis, respectively by flow cytometry analysis. The results of fluorescence microscopy and flow cytometry of SK-Mel 28 and HT-1080 upon treatment with PsPL8A (1.3 μM) for 24?h, gave green fluorescence due to dissipation of mitochondrial potential with JC-1 dye.Conclusions
Chondroitin AC lyase (PsPL8A) displayed anti-tumor potential against human melanoma SK-Mel 28 and fibrosarcoma HT-1080 cell lines, while the mouse fibroblast L929 cells were unaffected. 相似文献15.
Beata Wilenska Dagmara Tymecka Marcin Włodarczyk Aleksandra Sobolewska-Włodarczyk Maria Wiśniewska-Jarosińska Jolanta Dyniewicz Árpád Somogyi Jakub Fichna Aleksandra Misicka 《Pharmacological reports : PR》2019,71(1):42-47
Background
Inflammatory bowel diseases (IBD) are a group of chronic and recurrent gastrointestinal disorders that are difficult to control. Recently, a new IBD therapy based on the targeting of the endogenous opioid system has been proposed. Consequently, due to the fact that endogenous enkephalins have an anti-inflammatory effect, we aimed at investigating the degradation of serum enkephalin (Met- and Leu-enkephalin) in patients with IBD.Methods
Enkephalin degradation in serum of patients with IBD was characterized using mass spectrometry methods. Calculated half-life (T1/2) of enkephalins were compared and correlated with the disease type and gender of the patients. Additionally, statistical analysis was used to examine the dynamics of changes in terms of inhibition of enkephalins degradation within research groups.Results
Our research indicates that the degree of enkephalins degradation depends on the gender of the patients. The difference is most evident for the rate of Met-enkephalin degradation between men (mean T1/2?=?13.61?min) and women (mean T1/2 ?=?21.84?min) with Crohn’s disease (CD).Conclusions
The most significant alternation of enkephalins degradation in serum samples of IBD patients, compared to control group, were observed in both Crohn’s disease and ulcerative colitis (UC) female patients. We suggest that the differences observed between the genders in IBD patients may be explained by regulation of enkephalinases activity by estradiol. 相似文献16.
Jagoda Abramek Jacek Bogucki Marta Ziaja-Sołtys Andrzej Stępniewski Anna Bogucka-Kocka 《Pharmacological reports : PR》2019,71(2):248-256
Background
Sodium dichloroacetate (DCA) is an agent with anticancer properties against solid tumors. DCA also seems to have antileukemic activity. In order to affirm it we investigate the effect of DCA on cell viability and apoptotic gene expression profiles in leukemia cell lines: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2.Methods
Cell viability was assessed by trypan blue staining. The expression of 93 genes involved in the process of apoptosis was determined by real-time PCR method using Taqman Low Density Array (TLDA).Results
CEM/C1, CCRF/CEM, HL-60, HL-60/MX2 cells were exposed to DCA for 24?h. The sensitivity of each cell line to DCA is different and depends on the concentration. CEM/C1 was the most sensitive with an half-maximal inhibitory concentration (IC50) value of 30?mM, while HL-60/MX2 was the most resistant with an IC50 value of 75?mM. Exposure of leukemia cells to DCA causes differences in gene expression profiles which cannot indicate that any particular pathway of apoptosis is initiated. However, the presence of 388 statistically significant correlations between expression pattern of gens was determined.Conclusion
We showed that DCA causes a decrease in viability of leukemia cells. The decline depends on DCA concentration. The induction of any particular apoptosis pathway is not shown in cells after DCA treatment. For that reason, studies on the molecular mechanism of cell death after exposure to DCA should be continued. 相似文献17.
Background
Transient receptor potential ankyrin-1 (TRPA1) channels expressed in the central terminal of dorsal root ganglion neurons in the spinal substantia gelatinosa (SG) play a role in modulating nociceptive transmission. Although plant-derived compounds exhibiting antinociception (such as eugenol, carvacrol and thymol) activate TRPA1 channels to enhance spontaneous excitatory transmission while hyperpolarizing membranes in SG neurons without TRPA1 activation, specific chemical moieties involved in synaptic modulation are unknown.Methods
We examined the effects of other plant-derived compounds (guaiacol, vanillin, vanillic acid and p-cymene) on holding current and spontaneous excitatory transmission at ?70?mV by applying the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices.Results
None of the compounds affected the frequency or amplitude of spontaneous excitatory postsynaptic current. Guaiacol and vanillic acid had no effect on holding currents, while vanillin and p-cymene produced an inward and outward current, respectively, in some neurons tested. Synaptic modulation was also observed within the same neuron as the activities of eugenol, carvacrol, thymol, and the chemically-related plant-derived compound zingerone occurred.Conclusion
A substituted group in eugenol and zingerone, but not in guaiacol, vanillin or vanillic acid, as well as an OH bound to the benzene ring of carvacrol and thymol, but not p-cymene, play a role in producing outward current and TRPA1 activation. Thus, the binding of such chemical moeties to the benzene ring of plant-derived compounds appears necessary to modulate nociceptive transmission in the SG. This information provides insight for the development of new analgesics based on plant-derived compounds. 相似文献18.
Parham Jabbarzadeh Kaboli Melody Pui-Yee Leong Patimah Ismail King-Hwa Ling 《Pharmacological reports : PR》2019,71(1):13-23
Background
Berberine is an alkaloid plant-based DNA intercalator that affects gene regulation, particularly expression of oncogenic and tumor suppressor proteins. The effects of berberine on different signaling proteins remains to be elucidated. The present study aimed to identify the effects of berberine against key oncogenic proteins in breast cancer cells.Methods
Molecular docking and molecular dynamics simulations were used for EGFR, p38, ERK1/2, and AKT. The effects of berberine and lapatinib on MAPK and PI3K pathways in MDA-MB231 and MCF-7 cells were evaluated using immunoflorescence assays, and the amounts of phosphorylated kinases were compared to total kinases after treating with different concentrations of berberine.Results
Simulations showed berberine accurately interacted with EGFR, AKT, P38, and ERK1/2 active sites in silico (scores = -7.57 to -7.92 Kcal/mol) and decreased the levels of active forms of corresponding enzymes in both cell lines; however, berberine binding to p38 showed less stability. Cytotoxicity analysis indicated that MDA-MB231 cells were resistant to berberine compared to MCF-7 cells [72?h IC50?=?50 versus 15 μM, respectively). Also, lapatinib strongly activated AKT but suppressed EGFR in MDA-MB231 cells. The activity of EGFR, AKT, P38, and ERK1/2 were affected by berberine; however, berberine dramatically reduced EGFR and AKT phosphorylation.Conclusion
By way of its multikinase inhibitory effects, berberine might be a useful replacement for lapatinib, an EGFR inhibitor which can cause acquired drug resistance in patients. 相似文献19.
Reem Elkholy Mohamed Balaha Noha El-Anwar Samah Kandeel Sabiha Hedya Mohamed-Nabih Abd-El Rahman 《Pharmacological reports : PR》2019,71(2):330-337
Background
Food allergy (FA) is a worldwide health problem, affecting nearly 10% of all populations, with no prophylactic options or regulatory treatment available until now. Fisetin, a biologically active flavonoid, and telmisartan, the highly selective competitive AT1 receptor antagonist, recently exhibited potent anti-inflammatory and immunomodulatory activities. In the present study, we have evaluated the possible anti-inflammatory and immunomodulatory activities of fisetin and telmisartan each alone or in low-dose combination in a mouse model of FA.Methods
For induction of FA, eight-week-old BALB/c mice, sensitized by two ip injection of 50 μg ovalbumin (OVA) and 1?mg alum at day 0 and 7. Then, each mouse challenged with 10 mg OVA at days 14, 16, 18, and 21. On the 28th day, the fifth challenge carried out by oral administration of 50?mg OVA. Either fisetin (1 or 3?mg/kg/d), telmisartan (1 or 3?mg/kg/d) or a combination of fisetin 1?mg/kg/d and telmisartan 1?mg/kg/d received orally from the 13th day till 28th day. In challenge days, the treatments received one-hour before the challenge.Results
Our data showed that fisetin and telmisartan each alone or in low-dose combination attenuated the anaphylactic manifestation, decreased blood eosinophilic count, serum OVA-specific IgE, and IL-4 levels, the intestinal total and degranulated mast cells count, and CD4+ immunohistochemical expression. Furthermore, they enhanced the serum IFN-γ level and abrogated the intestinal histopathological changes induced by OVA in mice.Conclusion
Either fisetin, telmisartan or their low-dose combination could be promising in the management of FA. 相似文献20.
Jarogniew J. Łuszczki Paweł Marzeda Agata Gut-Lepiech Maria W. Kondrat-Wróbel Paula Wróblewska-Łuczka Sławomir Karwan Tomasz Plech 《Pharmacological reports : PR》2019,71(2):299-305