Med Sci Monit Basic Res
· 2017 Jun · PMID 28615615
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BACKGROUND Macrophages are highly heterogeneous and plastic cells that are involved in all stages of atherogenesis. They can undergo polarization by shifting between M1 and M2 functional phenotypes. However, the role of...BACKGROUND Macrophages are highly heterogeneous and plastic cells that are involved in all stages of atherogenesis. They can undergo polarization by shifting between M1 and M2 functional phenotypes. However, the role of macrophage polarization and the molecular mechanism in modulating atherosclerotic plaque stability remain incompletely understood. Our study investigated the role of STAT6 in regulating macrophage phenotypes to affect atherosclerotic plaque stability. MATERIAL AND METHODS A murine atherosclerosis model with vulnerable plaques was induced with high-cholesterol diet and PCCP surgeries in ApoE-/- mice. Murine macrophages RAW264.7 treated with ox-LDL or IL-4 were used to simulate the in vitro process. pcDNA3.1(-)/STAT6-expressing vectors were transfected into RAW264.7 to evaluate its effect on cell polarization and the involved molecules. RESULTS Unstable plaques presented significantly increased M1 markers (CD86 and iNOS) and less M2 markers (Arg-1 and TGF-β) than the stable plaques. Moreover, we found that STAT6 and p-STAT6 were greatly decreased in the vulnerable plaques and ox-LDL-induced macrophages, while their expression was elevated after IL-4 stimulation. The overexpression of STAT6 substantially reversed the ox-LDL-stimulated macrophage apoptosis and lipid accumulation. STAT6 upregulation promoted the differentiation of macrophage to M2 subtype as reflected by the increased expression of Arg-1 and TGF-β. Furthermore, we found that STAT6 overexpression activated the Wnt-β-catenin signaling by enhancing the translocation of β-catenin, while β-catenin suppression inhibited STAT6 overexpression-induced M2 polarization. CONCLUSIONS STAT6 facilitated atherosclerotic plaque stabilization by promoting the polarization of macrophages to M2 subtype and antagonizing ox-LDL-induced cell apoptosis and lipid deposition in a Wnt-β-catenin-dependent manner.
Med Sci Monit Basic Res
· 2017 May · PMID 28522796
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BACKGROUND There is a long-standing debate about the role of beta-adrenoceptor polymorphisms in the cardiovascular system. We wanted to elucidate whether β1-adrenoceptor-polymorphisms affects the postoperative catecholam...BACKGROUND There is a long-standing debate about the role of beta-adrenoceptor polymorphisms in the cardiovascular system. We wanted to elucidate whether β1-adrenoceptor-polymorphisms affects the postoperative catecholamine consumption and the length of intermediate care unit stay in patients undergoing cardiac surgery, and whether this might be enhanced or attenuated by catechol-O-methyl-transferase (COMT) polymorphism. MATERIAL AND METHODS We included 116 patients (63±1.2 years; 34% females; 81±1 kg) undergoing cardiac surgery. We assessed Arg389Gly and Ser49Gly-β1-adrenoceptor (B1AR) polymorphism together with Val158Met-COMT polymorphism by real-time PCR using fluorescence resonance energy transfer (PCR-FRET). The preoperative risk was assessed by EuroSCORE. In addition, we measured the endogenous preoperative epinephrine and norepinephrine plasma concentrations using an electrochemical HPLC method. RESULTS 84.6% were homozygous for Ser49Ser, 52.1% homozygous for Arg389Arg B1AR, and 32.5% for Val158Val-COMT, while 15.4% showed Ser49Gly B1AR, 38.5% Arg389Gly-B1AR, and 35.6% Val158Met-COMT. We found that the Gly49-variant, the Gly389-variant, and the Val158-COMT-variant were associated with higher postoperative norepinephrine consumption. All patients carrying the Val158-COMT allele exhibited higher preoperative norepinephrine concentrations. Moreover, we found that both β1-adrenoceptor polymorphisms were associated with a longer stay in hospital, which was modulated by the COMT polymorphism. CONCLUSIONS These data show that the β1-adrenoceptor polymorphisms, together with the COMT polymorphism, affect norepinephrine consumption and stay in hospital in a situation of enhanced cardiovascular stress, reflected here by the postoperative period after cardiac surgery. Moreover, we conclude that patients with the Val158-COMT genotype exhibit higher endogenous resting plasma norepinephrine levels.
Weymann A, Ali-Hasan-Al-Saegh S, Sabashnikov A
… +23 more, Popov AF, Mirhosseini SJ, Liu T, Lotfaliani M, Sá MPBO, Baker WLL, Yavuz S, Zeriouh M, Jang JS, Dehghan H, Meng L, Testa L, D'Ascenzo F, Benedetto U, Tse G, Nombela-Franco L, Dohmen PM, Deshmukh AJ, Linde C, Biondi-Zoccai G, Stone GW, Calkins H, Surgery And Cardiology-Group Imcsc-Group IMOC
Med Sci Monit Basic Res
· 2017 May · PMID 28496093
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BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and...BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and is routinely used in the workup of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of hematological parameters in the CBC test with new-onset and recurrent AF. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating hematologic parameters in patients with new-onset AF and recurrent AF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS The literature search of all major databases retrieved 2150 studies. After screening, 70 studies were analyzed in the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of -26.39×10^9/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001), white blood cell (WBC) (WMD=-0.005×10^9/L and p=0.83), neutrophil to lymphocyte ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW) (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF revealed PC (WMD=-2.71×109/L and p=0.59), WBC (WMD=0.20×10^9/L (95% CI: 0.08 to 0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001). CONCLUSIONS Hematological parameters have significant ability to predict occurrence and recurrence of AF. Therefore, emphasizing the potential predictive role of hematological parameters for new-onset and recurrent AF, we recommend adding the CBC test to the diagnostic modalities of AF in clinical practice.
Med Sci Monit Basic Res
· 2017 May · PMID 28473687
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BACKGROUND The aim of this study was to explore the relationship between physical performance and BMI (body mass index) of university students in China. MATERIAL AND METHODS We conducted a cross-sectional study evaluatin...BACKGROUND The aim of this study was to explore the relationship between physical performance and BMI (body mass index) of university students in China. MATERIAL AND METHODS We conducted a cross-sectional study evaluating the physical performance and BMI of university students. BMI was calculated based on height and weight. Overweight and obesity were defined by the Working Group on Obesity references in China. RESULTS A total of 2313 participants (978 males and 1335 females) were recruited in our study. The mean value of the 50-meter dash and standing long jump in male students was higher than in female students (P<0.05). The overall prevalences of overweight (including obesity) and obesity for male students were 17.9% and 4.2%, respectively, and 5.1% and 0.5%, respectively, for female university students. BMI was weakly positively associated with the 50-meter dash score, but was negatively associated with the score for standing long jump and pull-ups. CONCLUSIONS Our study suggested that overweight and obesity are associated with physical performance of university students, especially in male students. University students should exercise more to improve physical health.
Zhu L, Ge F, Yang L
… +4 more, Li W, Wei S, Tao Y, Du G
Med Sci Monit Basic Res
· 2017 Apr · PMID 28450696
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BACKGROUND Alginate is a natural polysaccharide obtained from brown algae and has been shown to have numerous applications in biomedical science, such as wound healing, delivery of bioactive agents, and cell transplantat...BACKGROUND Alginate is a natural polysaccharide obtained from brown algae and has been shown to have numerous applications in biomedical science, such as wound healing, delivery of bioactive agents, and cell transplantation. Ovalbumin (OVA) peptide 323-339 has been reported to be involved in immune response. MATERIAL AND METHODS This work investigated the use of alginate particles as a carrier and adjuvant for the immune therapy of cancer. Alginate particles loaded with OVA peptide were produced via emulsion. A tumor model was established in C57BL/6J mice via subcutaneous injection of 3×105 B16-OVA tumor cells. The effect of alginate/OVA peptide on cell viability was analyzed by use of the CCK-8 assay kit. Activation of macrophages was examined by checking cell surface makers CD40 and CD86 by FACs. RESULTS Alginate/OVA peptide inhibited tumor progression more effectively than using the peptide alone. The viability and uptake study illustrated that this particle is safe and non-toxic. The activation study demonstrated that alginate particles can promote the activation of surface markers on macrophages. ELISA assay showed that the particles with peptide can promote the secretion of inflammatory and effector cytokines from macrophages. CONCLUSIONS This study demonstrated that alginate has dual functions in immune therapy of cancer, serving both as a carrier and an adjuvant.
Niu H, Xu M, Li S
… +5 more, Chen J, Luo J, Zhao X, Gao C, Li X
Med Sci Monit Basic Res
· 2017 Apr · PMID 28408733
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BACKGROUND Neoangiogenesis occurring in inflamed articular synovium in early rheumatoid arthritis (RA) is characterized by enhanced vascular permeability that allows nanoparticle agents, including liposomes, to deliver e...BACKGROUND Neoangiogenesis occurring in inflamed articular synovium in early rheumatoid arthritis (RA) is characterized by enhanced vascular permeability that allows nanoparticle agents, including liposomes, to deliver encapsulated drugs to arthritic joints and subsequently improve therapeutic efficacy and reduce adverse effects. However, the targeting distribution of liposomes in arthritic joints during RA has not been quantitatively demonstrated. We performed this study to evaluate the targeting distribution of PEGylated doxorubicin liposomes in the arthritic joints of collagen-induced arthritis (CIA) rats by high-performance liquid chromatography (HPLC). MATERIAL AND METHODS Two doxorubicin formulations were administered to CIA rats via tail intravenous injection at a single dose (50 mg/m²). CIA rats were sacrificed and the tissues of the inflamed ankle joints were collected. The content of doxorubicin in the arthritic joints was analyzed by a validated and reproducible HPLC method. A two-way ANOVA for 2×5 factorial design was used for statistical analysis. RESULTS The developed HPLC method was sensitive, precise, and reproducible. The method was successfully applied to quantify doxorubicin content in arthritic tissues. At each time point (6, 12, 24, 48, and 72 h), doxorubicin content in the arthritic joints of the doxorubicin liposome group (DOX-LIP group) was higher than in the free doxorubicin group (DOX group) (P<0.05). In the DOX-LIP group, doxorubicin levels in the arthritic joints increased gradually and significantly in the interval of 6-72 h post-administration. CONCLUSIONS PEGylated doxorubicin liposomes were targeted to, accumulated, and retained in the arthritic joints of CIA rats. The present study indicates that liposome encapsulation increases the therapeutic efficacy of antirheumatic drugs, presenting a promising therapeutic strategy for RA.
Tang D, Tao D, Fang Y
… +3 more, Deng C, Xu Q, Zhou J
Med Sci Monit Basic Res
· 2017 Apr · PMID 28386055
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BACKGROUND Recent evidence reveals that the inflammatory microenvironment is associated with tumor migration, invasion, and metastasis. Tumor necrosis factor-α (TNF-α) play a vital role in regulation of the inflammatory...BACKGROUND Recent evidence reveals that the inflammatory microenvironment is associated with tumor migration, invasion, and metastasis. Tumor necrosis factor-α (TNF-α) play a vital role in regulation of the inflammatory process in tumor development. Nuclear factor-kappa B (NF-κB) is one of the key transcription factors which regulate processes in tumor promotion. The aim of this study was to explore the role of NF-κB on the invasion and migration of oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS The IKKβ and p65 mRNA and protein levels were determined by quantitative RT-PCR and western blot. Wound scratch healing assays and transwell migration assays were used to evaluate the effect of TNF-α and BAY11-7082 on the migration of the OSCC cell lines (HN4, HN6, and CAL27). RESULTS We observed a significant increase of the expression level of IKKβ and p65 in OSCC cells from the experimental group at 24 h, 48 h, and 72 h after TNF-α stimulation. Invasion and metastasis of OSCC cells was obviously improved after the TNF-α stimulation. Invasion and metastasis ability of OSCC cells was inhibited in the suppression group, and no significant changes were observed in expression level of IKKβ and p65 after the use of BAY11-7082. CONCLUSIONS Our results suggest that TNF-α enhances the invasion and metastasis ability of OSCC cells via the NF-κB signaling pathway.
Weymann A, Sabashnikov A, Ali-Hasan-Al-Saegh S
… +17 more, Popov AF, Jalil Mirhosseini S, Baker WL, Lotfaliani M, Liu T, Dehghan H, Yavuz S, de Oliveira Sá MP, Jang JS, Zeriouh M, Meng L, D'Ascenzo F, Deshmukh AJ, Biondi-Zoccai G, Dohmen PM, Calkins H, Cardiac Surgery And Cardiology-Group Imcsc-Group IM
Med Sci Monit Basic Res
· 2017 Mar · PMID 28360407
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BACKGROUND The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the role of prothrombotic markers in AF remains inconclusi...BACKGROUND The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the role of prothrombotic markers in AF remains inconclusive. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating the association of coagulation activation, fibrinolytic, and endothelial function with occurrence of AF and clinical adverse events. A comprehensive subgroup analysis and meta-regression was performed to explore potential sources of heterogeneity. RESULTS A literature search of major databases retrieved 1703 studies. After screening, a total of 71 studies were identified. Pooled analysis showed the association of coagulation markers (D-dimer (weighted mean difference (WMD) =197.67 and p<0.001), fibrinogen (WMD=0.43 and p<0.001), prothrombin fragment 1-2 (WMD=0.53 and p<0.001), antithrombin III (WMD=23.90 and p=0.004), thrombin-antithrombin (WMD=5.47 and p=0.004)); fibrinolytic markers (tissue-type plasminogen activator (t-PA) (WMD=2.13 and p<0.001), plasminogen activator inhibitor (WMD=11.44 and p<0.001), fibrinopeptide-A (WMD=4.13 and p=0.01)); and endothelial markers (von Willebrand factor (WMD=27.01 and p<0.001) and soluble thrombomodulin (WMD=3.92 and p<0.001)) with AF. CONCLUSIONS The levels of coagulation, fibrinolytic, and endothelial markers have been reported to be significantly higher in AF patients than in SR patients.
Fayyad-Kazan M, Najar M, Fayyad-Kazan H
… +2 more, Raicevic G, Lagneaux L
Med Sci Monit Basic Res
· 2017 Mar · PMID 28336906
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BACKGROUND Mesenchymal stromal cells (MSCs) possess potent immunomodulatory properties that increase their value as a cell-based therapeutic tool for managing various immune-based disorders. Over the past years, accumula...BACKGROUND Mesenchymal stromal cells (MSCs) possess potent immunomodulatory properties that increase their value as a cell-based therapeutic tool for managing various immune-based disorders. Over the past years, accumulated results from trials using MSCs-based therapy have shown substantial contradictions. Although the reasons underlying these discrepancies are still not completely understood, it is well known that the immunomodulatory activities mediated by distinct MSCs differ in a manner dependent on their tissue origin and adequate response to inflammation priming. Thus, characterization of new molecular pathway(s) through which distinct MSC populations can exert their immunomodulatory effects, particularly during inflammation, will undoubtedly enhance their therapeutic potential. MATERIAL AND METHODS After confirming their compliance with ISCT criteria, quantitative real time-PCR (qRT-PCR) was used to screen new immunoregulatory genes in MSCs, derived from adipose tissue, foreskin, Wharton's jelly or the bone-marrow, after being cultivated under normal and inflammatory conditions. RESULTS FGL2, GAL, SEMA4D, SEMA7A, and IDO1 genes appeared to be differentially transcribed in the different MSC populations. Moreover, these genes were not similarly modulated following MSCs-exposure to inflammatory signals. CONCLUSIONS Our observations suggest that these identified immunoregulatory genes may be considered as potential candidates to be targeted in order to enhance the immunomodulatory properties of MSCs towards more efficient clinical use.
Weymann A, Ali-Hasan-Al-Saegh S, Sabashnikov A
… +21 more, Popov AF, Mirhosseini SJ, Nombela-Franco L, Testa L, Lotfaliani M, Zeriouh M, Liu T, Dehghan H, Yavuz S, de Oliveira Sá MP, Baker WL, Jang JS, Gong M, Benedetto U, Dohmen PM, D'Ascenzo F, Deshmukh AJ, Biondi-Zoccai G, Calkins H, Stone GW, Surgery And Cardiology-Group Imcsc-Group IM
Med Sci Monit Basic Res
· 2017 Mar · PMID 28302997
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BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional characteristics including platelet count (PC), MPV, plat...BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional characteristics including platelet count (PC), MPV, platelet distribution width (PDW), platelet factor 4, beta thromboglobulin (BTG), and p-selectin with the occurrence of atrial fibrillation (AF) and consequent stroke. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating platelet characteristics in patients with paroxysmal, persistent and permanent atrial fibrillations. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS Literature search of all major databases retrieved 1,676 studies. After screening, a total of 73 studies were identified. Pooled analysis showed significant differences in PC (weighted mean difference (WMD)=-26.93 and p<0.001), MPV (WMD=0.61 and p<0.001), PDW (WMD=-0.22 and p=0.002), BTG (WMD=24.69 and p<0.001), PF4 (WMD=4.59 and p<0.001), and p-selectin (WMD=4.90 and p<0.001). CONCLUSIONS Platelets play a critical and precipitating role in the occurrence of AF. Whereas distribution width of platelets as well as factors of platelet activity was significantly greater in AF patients compared to SR patients, platelet count was significantly lower in AF patients.
Liu L, Zhan P, Nie D
… +4 more, Fan L, Lin H, Gao L, Mao X
Med Sci Monit Basic Res
· 2017 Mar · PMID 28280257
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BACKGROUND Accumulating data point to intermediate-conductance calcium-activated potassium channel (IKCa1) as a key player in controlling cell cycle progression and proliferation of human cancer cells. However, the role...BACKGROUND Accumulating data point to intermediate-conductance calcium-activated potassium channel (IKCa1) as a key player in controlling cell cycle progression and proliferation of human cancer cells. However, the role that IKCa1 plays in the growth of human cervical cancer cells is largely unexplored. MATERIAL AND METHODS In this study, Western blot analysis, immunohistochemical staining, and RT-PCR were first used for IKCa1protein and gene expression assays in cervical cancer tissues and HeLa cells. Then, IKCa1 channel blocker and siRNA were employed to inhibit the functionality of IKCa1 and downregulate gene expression in HeLa cells, respectively. After these treatments, we examined the level of cell proliferation by MTT method and measured IKCa1 currents by conventional whole-cell patch clamp technique. Cell apoptosis was assessed using the Annexin V-FITC/Propidium Iodide (PI) double-staining apoptosis detection kit. RESULTS We demonstrated that IKCa1 mRNA and protein are preferentially expressed in cervical cancer tissues and HeLa cells. We also showed that the IKCa1 channel blocker, clotrimazole, and IKCa1 channel siRNA can be used to suppress cervical cancer cell proliferation and decrease IKCa1 channel current. IKCa1 downregulation by specific siRNAs induced a significant increase in the proportion of apoptotic cells in HeLa cells. CONCLUSIONS IKCa1 is overexpressed in cervical cancer tissues, and IKCa1 upregulation in cervical cancer cell linea enhances cell proliferation, partly by reducing the proportion of apoptotic cells.
Ihana-Sugiyama N, Yamamoto-Honda R, Sugiyama T
… +3 more, Tsujimoto T, Kakei M, Noda M
Med Sci Monit Basic Res
· 2017 Feb · PMID 28242866
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BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patient...BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6%; fat, 43.2%). Self-monitoring blood glucose levels were measured at 0, 30, 60, and 120 min after the meal tests, and the increase in the postprandial area under the curve (AUC)0-120 min was determined. The HbA1c, glycated albumin, and 1,5-anhydroglucitol (AG) levels were measured, and continuous glucose monitoring was performed. RESULTS The increase in the postprandial AUC0-120 min was significantly smaller in the M+V group than in the L group after both meals. The 24-h average, 24-h standard deviations, 24-h AUC, and mean amplitude of glycemic excursion (MAGE) were similar for both groups and after both meals. The change in 1,5-AG was higher in the M+V group than in the L group. CONCLUSIONS The combination of M+V with basal therapy improved postprandial glucose excursion more effectively than L in T2DM patients.
Bashir S, Alghamd F, Alhussien A
… +4 more, Alohali M, Alatawi A, Almusned T, Habib SS
Med Sci Monit Basic Res
· 2017 Feb · PMID 28223681
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BACKGROUND Smoking is the predominant form of tobacco consumption and is growing worldwide, particularly in the younger generation in the Middle-East. We aimed to determine the effects of tobacco smoking on cognitive fun...BACKGROUND Smoking is the predominant form of tobacco consumption and is growing worldwide, particularly in the younger generation in the Middle-East. We aimed to determine the effects of tobacco smoking on cognitive functions among young Saudi adults. MATERIAL AND METHODS We recruited a group of cigarette smokers (N=22) and a group of controls (non-smokers) (N=30) from apparently healthy male volunteers aged 18-29 years. Cognitive function was assessed by using the Cambridge Neuropsychological Automated Battery (CANTAB). The cognitive functions outcome variables were the response time (attention-switching task [AST]), and the percentage of correct response (pattern recognition memory [PRM] task). Clinical, demographic, blood markers (brain-derived neurotrophic factor (BDNF) and apolipoprotein E) were assessed between groups. RESULTS The 2 groups were matched for age and educational status. In comparison to the control group, smokers showed significant cognitive impairments in AST-Latency (p=0.001), AST-Congruent (p=0.001), and AST-Incongruent condition (p=0.001). There was not significant difference in BDNF APOE serum level between the 2 groups. CONCLUSIONS These results indicate that attention and alertness were significantly impaired in smokers compared to non-smokers.
Chu L, Shen K, Liu P
… +5 more, Ye K, Wang Y, Li C, Kang X, Song Y
Med Sci Monit Basic Res
· 2017 Feb · PMID 28179618
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BACKGROUND It has been unclear whether relatively high cortisol and cortisone levels are related to overweight in childhood, parental body mass index (BMI), and family dietary habits. The aim of this study was to compare...BACKGROUND It has been unclear whether relatively high cortisol and cortisone levels are related to overweight in childhood, parental body mass index (BMI), and family dietary habits. The aim of this study was to compare cortisol and cortisone levels in urine and saliva from overweight and normal children, as well as correlations between children's BMI, parental BMI and family dietary behavior questionnaire score (QS). MATERIAL AND METHODS We analyzed the data from 52 overweight children and 53 age- and sex-matched normal-weight children aged 4-5 years. The concentrations of salivary cortisol (SF), salivary cortisone (SE), urinary cortisol (UF) and urinary cortisone (UE) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The family dietary behavior QS was answered by the parent mainly responsible for the family diet. RESULTS Average cortisol and cortisone levels were significantly higher in overweight children. There was no significant difference in the ratio of cortisol to cortisone (Rcc) and the marker of 11b-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activities. The results displayed correlations among cortisol, cortisone, and Rcc. Positive correlations were weak-to-moderate between BMI and SF, SE, UF, and UE. There were correlations between BMI and maternal BMI (mBMI), and BMI was significantly associated with QS. CONCLUSIONS Our results suggest that cortisol and cortisone levels are associated with overweight in children, but the 11β-HSD2 activities showed no significant differences. Unhealthy family diet was associated with higher BMI, UF, and UE, and families with maternal overweight or obesity had a higher prevalence of children's overweight or obesity.
Williamson CR, Khurana S, Nguyen P
… +2 more, Byrne CJ, Tai TC
Med Sci Monit Basic Res
· 2017 Jan · PMID 28138124
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BACKGROUND The renal renin-angiotensin system (RAS) is physiologically important for blood pressure regulation. Altered regulation of RAS-related genes has been observed in an animal model of hypertension (spontaneously...BACKGROUND The renal renin-angiotensin system (RAS) is physiologically important for blood pressure regulation. Altered regulation of RAS-related genes has been observed in an animal model of hypertension (spontaneously hypertensive rats - SHRs). The current understanding of certain RAS-related gene expression differences between Wistar-Kyoto rats (WKYs) and SHRs is either limited or has not been compared. The purpose of this study was to compare the regulation of key RAS-related genes in the kidneys of adult WKYs and SHRs. MATERIAL AND METHODS Coronal sections were dissected through the hilus of kidneys from 16-week-old male WKYs and SHRs. RT-PCR analysis was performed for Ace, Ace2, Agt, Agtr1a, Agtr1b, Agtr2, Atp6ap2 (PRR), Mas1, Ren, Rnls, and Slc12a3 (NCC). RESULTS Increased mRNA expression was observed for Ace, Ace2, Agt, Agtr1a, Agtr1b, and Atp6ap2 in SHRs compared to WKYs. Mas1, Ren, Slc12a3, and Rnls showed no difference in expression between animal types. CONCLUSIONS This study shows that the upregulation of several key RAS-related genes in the kidney may account for the increased blood pressure of adult SHRs.
Kalish S, Lyamina S, Manukhina E
… +3 more, Malyshev Y, Raetskaya A, Malyshev I
Med Sci Monit Basic Res
· 2017 Jan · PMID 28123171
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BACKGROUND M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the probl...BACKGROUND M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo. MATERIAL AND METHODS Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice. RESULTS 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect. CONCLUSIONS Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising.
Zembala-Szczerba M, Jaworowski A, Huras H
… +2 more, Babczyk D, Jach R
Med Sci Monit Basic Res
· 2017 Jan · PMID 28077838
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BACKGROUND Obesity is a major clinical problem. The number of obese pregnant women is rising rapidly. The consequences of obesity are significant and affect every aspect of perinatal care for both the mother and the deve...BACKGROUND Obesity is a major clinical problem. The number of obese pregnant women is rising rapidly. The consequences of obesity are significant and affect every aspect of perinatal care for both the mother and the developing fetus. Adipose tissue may be responsible for chronic subclinical inflammation in obesity, being a source of inflammatory mediators. The study was designed to evaluate the analysis of the serum concentration of inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and adiponectin, in obese pregnant women at full-term pregnancies. MATERIAL AND METHODS The study included 40 women with body mass index (BMI) less than 30 and 24 pregnant women with BMI equal to or greater than 30, admitted to the Perinatology and Obstetrics Department of the University Hospital in Cracow in the first stage of labor. Blood samples were taken from patients to detect the serum concentration of cytokines. Ultrasound was used to evaluate the development of the fetus, including estimated fetal weight, Doppler flows, and the amount of amniotic fluid. We also included the history of chronic diseases and other complications of the pregnancy. A p-value <0.05 was considered significant. RESULTS The level of adiponectin in obese patients as compared to controls was significantly lower. There was no statistically significant difference in either group when TNF-α and IL-6 were measured. The results of the survey are consistent with previous reports. CONCLUSIONS The exact role of inflammation in pregnancy is not well understood. Determining the exact functions of the different cytokines in physiological pregnancy and pregnancy complicated by obesity requires further study.
Med Sci Monit Basic Res
· 2016 Dec · PMID 28033308
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BACKGROUND The aim of this study was to explore the neural protective effect of polysaccharide of Gastrodia elata Blume (PGB) and electro-acupuncture (EA) on focal cerebral ischemia rats. MATERIAL AND METHODS A total of...BACKGROUND The aim of this study was to explore the neural protective effect of polysaccharide of Gastrodia elata Blume (PGB) and electro-acupuncture (EA) on focal cerebral ischemia rats. MATERIAL AND METHODS A total of 40 Sprague-Dawley rats were randomly divided into 5 groups (normal group, model group, PGB group, EA group and PGB+EA group). The model was prepared by middle cerebral artery occlusion (MCAO). Two week after modeling, rats were given PGB, EA, or a combination of the 2 in continuous treatment for 2 successive weeks. 14 days after modeling, expressions of BDNF and SCF protein in the caudate putamen (CPu) were detected by immunohistochemistry. RESULTS Positive expression of BDNF and SCF protein was found in the right caudate putamen of each group of rats. Expressions of BDNF and SCF in the CPu of the model group were higher than normal group (P<0.05). Compared with the model group, the expressions of BDNF and SCF in the CPu of the PGB group, the EA group, and the PGB plus EA group increased significantly (P<0.05). The expressions of BDNF and SCF obviously increased in the PGB plus EA group compared to those of the EA group and the PGB group (P<0.05). CONCLUSIONS PGB and EA up-regulated the expressions of BDNF and SCF protein in the CPu of focal cerebral ischemia rats, and the combination of PGB+EA has a synergistic effect on the recovery from cerebral ischemia.