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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.
Zuyue Chen Hong Wei Boriss Sagalajev Ari Koivisto Antti Pertovaara 《Pharmacological reports : PR》2019,71(1):54-60
Background
The central amygdaloid nucleus (CeA) is involved in processing and descending regulation of pain. Amygdaloid mechanisms underlying pain processing and control are poorly known. Here we tested the hypothesis that perioperative CeA administration of tetrapentylammonium (TPA), a non-selective THIK-1 channel blocker and thereby inhibitor of microglia, attenuates development of chronic neuropathic pain and comorbid anxiety-like behavior.Methods
Rats with a spared nerve injury (SNI) model of neuropathy or sham operation had a chronic cannula for drug microinjections into the CeA or a control injection site. Monofilament test was used to evaluate pain, and light-dark box (LDB) to assess anxiety.Results
Perioperative CeA treatment with TPA (30?μg/day up to the third postoperative day, D3) significantly attenuated the development of pain and anxiety-like behavior. In the late phase (> D14), CeA administration of TPA (3–30?μg) failed to influence pain. Perioperative minocycline (microglia inhibitor; 25?μg), MK-801 (an N-Methyl-D-aspartate receptor antagonist; 0.1?μg), vehicle or TPA in a control injection site failed to attenuate pain development.Conclusions
Perioperative treatment of the CeA with TPA delayed development of neuropathic pain and comorbid anxiety-like behavior, while TPA treatment failed to influence maintenance of established neuropathic pain. The failures to attenuate pain development with CeA administrations of minocycline or MK-801 do not support the hypothesis that the TPA-induced prophylactic effect was due to inhibition of amygdaloid microglia or N-methyl-D-aspartate receptors. While TPA in the CeA proved to have a prophylactic effect on SNI-induced pain behavior, the underlying mechanism still remains to be studied. 相似文献3.
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4.
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5.
Duygun Altıntaş Aykan Tuba Tulay Koca Selma Yaman Nadire Eser 《Pharmacological reports : PR》2019,71(2):306-310
Background
We hypothesized that renin-angiotensin system and neprilysin (NEP) inhibition can modulate the nociceptive parameters on hypertensive rats. The aim of this study is to assess the preventive and therapeutic effects of ramipril and sacubitril on the pain hypersensitivities, and their interaction mechanisms with high blood pressure.Methods
Antinociceptive effects of ramipril and sacubitril were compared with those of diclofenac. Threshold of pain assesments were recorded before drugs administration. After a 18 days treatment, normotensive and dexamethasone-induced hypertensive rats were evaluated on thermal hyperalgesia and mechanical allodynia tests. Blood pressure of rats were verified by mean arterial pressure measurement.Results
Hypertensive rats showed significantly high pain threshold on thermal plantar test compared to that of normotensives. Among hypertensive rats, pain hypersensitivity was lowest in diclofenac group, followed by sacubitril group, while ramipril caused increased thermal and mechanical hypersensitivities.Conclusion
We found that NEP inhibition may play a role in nociception in hypertensive rats. NEP inhibitors may be suitable choice for the management of hypertension and pain because of their therapeutic and preventive effects on nociception and arterial blood pressure. 相似文献6.
Insights into the structure and tubulin-targeted anticancer potential of N-(3-bromobenzyl) noscapine
Sanith Cheriyamundath Tejashree Mahaddalkar Praveen Kumar Reddy Nagireddy Balasubramanian Sridhar Srinivas Kantevari Manu Lopus 《Pharmacological reports : PR》2019,71(1):48-53
Background
Noscapine is a non-narcotic, antitussive alkaloid isolated from plants of Papaveraceae family. This benzylisoquinoline alkaloid and its synthetic derivatives, called noscapinoids, are being evaluated for their anticancer potential.Methods
The structure of a novel analogue, N-(3-bromobenzyl) noscapine (N-BBN) was elucidated by X-ray crystallography. Effect of N-BBN on cancer cell proliferation and cellular microtubules were studied by sulphorhodamine B assay and immunofluorescence, respectively. Binding interactions of the alkaloid with tubulin was studied using spectrofluorimetry.Results
N-BBN, synthesized by introducing modification at site B (‘N’ in isoquinoline unit) and a bromo group at the 9th position of the parent compound noscapine, was found to be superior to many of the past-generation noscapinoids in inhibiting cancer cell viability and it showed a strong inhibition of the clonogenic potential of an aggressively metastatic breast tumour cell line, MDA-MB-231. The compound perturbed the tertiary structure of purified tubulin as indicated by an anilinonaphthalene sulfonic acid-binding assay. However, substantiating the common feature of noscapinoids, it did not alter microtubule polymer mass considerably. In cells, the drug-treatment showed a peculiar type of disruption of normal microtubule architecture.Conclusion
N-BBN may be considered for further investigations as a potent antiproliferative agent. 相似文献7.
Iwona Majcher-Maślanka Anna Solarz Agnieszka Chocyk 《Pharmacological reports : PR》2019,71(2):347-350
Background
Corticosteroid-binding globulin (CBG), albumin and 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes play crucial roles in the bioavailability of glucocorticoids. Downstream of the adrenal glands, these proteins affect glucocorticoid levels in target tissues. Early-life stress (ELS) is known to program glucocorticoid action at many levels. The effects of ELS on the concentrations and synthesis of CBG and albumin and on the expression of 11β-HSD remain unclear.Methods
The maternal separation (MS) procedure in rats on postnatal days 1–14 was used as a model of ELS. On postnatal day 35 (adolescence), the serum corticosterone, CBG and albumin concentrations of male rats were measured by ELISA, while the mRNA and protein levels of CBG, albumin and 11β-HSD1 in the liver and brain were examined by RT-qPCR and Western blot, respectively.Results
Under basal conditions, MS rats displayed lower levels of serum CBG and albumin. However, MS did not affect CBG or albumin synthesis in the liver, suggesting that the half-life and/or secretion of these proteins were influenced by MS. Additionally, MS rats showed increased protein expression of 11β-HSD1, specifically in the medial prefrontal cortex.Conclusions
These results indicate that ELS may potentially program glucocorticoid action through its effects on glucocorticoid bioavailability in tissues. 相似文献8.
Background
Both selenium and vitamin D were found to reduce thyroid antibody titers in women with Hashimoto’s thyroiditis.Methods
The study enrolled 37 young drug-naïve euthyroid men with autoimmune thyroiditis, who were treated for 6 months with either exogenous vitamin D (group A, n?=?20) or selenomethionine (group B, n?=?17). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin and free thyroid hormones, serum levels of 25-hydroxyvitamin D, as well Jostel’s thyrotropin, the SPINA-GT and the SPINA-GD indices were determined at the beginning and at the end of the study.Results
At baseline, there were no differences between the study groups. Both vitamin D and selenomethionine reduced antibody titers and increased the SPINA-GT index. Only selenomethionine affected the SPINA-GD index, while only vitamin D increased 25-hydroxyvitamin D levels. Neither selenomethionine nor vitamin D significantly affected thyrotropin and free thyroid hormone levels. The effect of vitamin D on antibody titers correlated with baseline and treatment-induced changes in serum levels of 25-hydroxivitamin D.Conclusions
Both vitamin D and selenomethionine have a beneficial effect on thyroid autoimmunity in drug-naïve men with Hashimoto’s thyroiditis. 相似文献9.
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10.
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11.
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12.
Hubert Zatorski Maciej Salaga Marta Zielińska Andrzej Wasilewski Aleksandra Misicka Mariusz Sacharczuk Jakub Fichna 《Pharmacological reports : PR》2019,71(2):218-224
Background
Gastric mucosal injury appears when acid and pepsin production, simultaneously with inadequate mucosal response, overwhelms protective mechanism in stomach. Here we aimed to explore the linkage between gastric lesion formation and endogenous opioid system activity.Methods
Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low endogenous opioid system activity were used. Gastric mucosal injury was induced by ethanol (EtOH) and chronic mild stress. To investigate the anti-inflammatory effect of the endogenous opioid system macroscopic score, myeloperoxidase (MPO) activity, the expression of inflammatory molecules as well as oxidative stress markers were determined. Moreover, expression of opioid receptors μ (MOR), κ (KOR) and δ (DOR) at mRNA levels were determined in gastric tissue.Results
High activity of the endogenous opioid system alleviated gastric lesions development in the EtOH-and chronic mild stress-induced mouse gastric mucosal injury models, as demonstrated by decreased macroscopic score in HA line compared to LA. Additionally, antioxidative stress defence mechanisms were positively modulated in both models of gastric mucosal injury. MOR and partially KOR receptors may be responsible for the gastroprotective effect.Conclusion
To our knowledge this is the first study to show that increased activity of the endogenous opioid system prevents from gastric lesion formation by influencing – among others – the anti-inflammatory and anti-oxidant mechanisms in the mice stomach. Hence, we suggest that opioids may play an important role in gastric mucosal injury prevention. 相似文献13.
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14.
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15.
Lutiana R. Simões Soraia Netto Jaqueline S. Generoso Renan A. Ceretta Rodrigo F. Valim Diogo Dominguini Monique Michels Gislaine Z. Réus Samira S. Valvassori Felipe Dal-Pizzol Tatiana Barichello 《Pharmacological reports : PR》2019,71(1):24-31
Background
A periodontal lesion is a consequence of chronic inflammatory processes, itself triggered by a bacterial infection of the pulpal and endodontic microenvironment. Evidence suggests that periodontal lesion induction could alter inflammatory cytokines leading to behavior changes. These effects in the context of anxiety and depressive behavior have been not full investigated. We aimed to observe anxiety- and depressive-like behavioral in rodent subjected to periapical dental lesions.Methods
Pro-inflammatory cytokines levels also were investigated in the frontal cortex and hippocampus. Parameters related to hypothalamic–pituitary–adrenal (HPA) axis activation also were evaluated. Wistar rats were divided in groups: control/saline; control/imipramine; periapical lesion/saline; and periapical lesion/imipramine. Three weeks after induction of the periapical dental lesion, they were subjected to behavioral tests.Results
In the periapical lesion group was demonstrated anhedonic behavior and depressive-like behavior. In the elevated plus-maze test the periapical lesion group had an increase in the number of entries and spent more time in the closed arms. Imipramine treatment was able to reverse depressive- and anxiety-like behaviors. In the hippocampus and frontal cortex tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and serum adrenocorticotropic hormone (ACTH) levels were higher in the periapical lesion group. However, rats treated with imipramine had lower IL-1β and ACTH levels.Conclusions
Our results revealed depressive- and anxiety-like behaviors following induction of a specific dental lesion. These effects could be associated to higher levels of brain pro-inflammatory cytokines and HPA axis changes. Antidepressants treatments could be an alternative to treat comorbidities associated to periodontal lesions. 相似文献16.
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17.
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18.
Background
Both exogenous vitamin D and selenium reduce thyroid antibody titers. The aim of the study was to investigate whether the impact of vitamin D on thyroid autoimmunity is affected by selenium intake.Methods
The study included 47 euthyroid women with Hashimoto’s thyroiditis and low vitamin D status, 23 of whom had been treated with selenomethionine (200?μg daily) for at least 12 months before the beginning of the study. During the study, all patients were treated with vitamin D preparations (4000 IU daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, as well as circulating levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D were measured before vitamin D supplementation and 6 months later. Moreover, at the beginning and at the end of the study, we calculated Jostel’s thyrotropin index, the SPINA-GT index and the SPINA-GD index.Results
With the exception of the free triiodothyronine/free thyroxine ratio and the SPINA-GD index, there were no differences between the study groups. In both groups, vitamin D increased 25-hydroxyvitamin D levels, reduced thyroid peroxidase and thyroglobulin antibody titers, as well as increased the SPINA-GT index. The effects on antibody titers and the SPINA-GT index were more pronounced in women receiving selenomethionine. Neither in selenomethionine-treated nor in selenomethionine-naïve women vitamin D affected serum hormone levels, Jostel’s index and the SPINA-GD index.Conclusions
The results of the study suggest that selenium intake enhances the effect of vitamin D on thyroid autoimmunity. 相似文献19.
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20.
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