Med Sci Monit Basic Res [JOURNAL]
Sun
200 papers
To Explore the Mechanism of the GRM4 Gene in Osteosarcoma by RNA Sequencing and Bioinformatics Approach.
Pang Y, Zhao J, Fowdur M … +3 more , Liu Y, Wu H, He M
Med Sci Monit Basic Res · 2018 Jan · PMID 29339716 · Full text
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERI...
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of the highest GRM4 expression were transfected with lentivirus-mediated small interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4 gene silencing were screened through RNA sequencing, and analyzed by bioinformatics. Additionally, the transcription factors (TFs) targeting GRM4 were predicted and the downstream protein-protein interaction (PPI) network was constructed using the bioinformatics approach. RESULTS A total of 51 significant DEGs were obtained, including 14 upregulated and 37 downregulated DEGs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs indicated that four significant enrichment pathways were obtained. A total of six TFs that could be involved in the transcriptional regulation of GRM4 were detected. The results showed that 182 genes in the PPI network were significantly enriched in 14 pathways. The chemokines and chemokine receptors were found to be significantly enriched in three pathways. CONCLUSIONS The DEGs in the four significant enrichment pathways might participate in the development and progression of osteosarcoma through GRM4. The results revealed that EGR1 and CTCF are probably involved in the transcriptional regulation of GRM4, which participates in the progress of osteosarcoma by interacting with chemokines and their receptors.
Factors Causing Disagreement between Measured and Calculated Low Density Lipoprotein-Cholesterol (LDL-C) in Clinical Laboratory Services.
Lekskulchai V
Med Sci Monit Basic Res · 2018 Jan · PMID 29326417 · Full text
BACKGROUND Since measured low density lipoprotein-cholesterol (LDL-C) has been available in clinical laboratories, there have been concern about the disagreement between measured and calculated LDL-C and the factors caus...
BACKGROUND Since measured low density lipoprotein-cholesterol (LDL-C) has been available in clinical laboratories, there have been concern about the disagreement between measured and calculated LDL-C and the factors causing their disagreement. MATERIAL AND METHODS Serum lipid concentrations were collected from 1,339 medical records of patients admitted to hospital between 2013 and 2015. They were grouped by their total cholesterol (TC), triglycerides (TG), and high-density lipoprotein-cholesterol (HDL-C) concentrations and the agreement between measured and calculated LDL-C was statistically analyzed. RESULTS A strong relationship was found between measured and calculated LDL-C. Significantly disagreements between measured and calculated LDL-C were found in all groups in 2013 and 2014 when lipids were analyzed by Cobas C501. Disagreements found in groups of low TG and low HDL-C concentrations in 2015 were when lipids were analyzed by Abbott Architect ci8200. In groups of calculated LDL-C <1.81 mmol/L, around 80% had the measured LDL-C >1.81 mmol/L. Among various atherogenic indices, non-HDL-C showed the strongest relationship with LDL-C, while TC to HDL-C ratio showed the strongest agreement with the LDL-C. CONCLUSIONS The disagreement between measured and calculated LDL-C in a clinical laboratory seemed to depend on the analytical system used, and was probably associated with individual laboratory variations.
Phlorizin Exerts Direct Protective Effects on Palmitic Acid (PA)-Induced Endothelial Dysfunction by Activating the PI3K/AKT/eNOS Signaling Pathway and Increasing the Levels of Nitric Oxide (NO).
Li CY, Wang LX, Dong SS … +4 more , Hong Y, Zhou XH, Zheng WW, Zheng C
Med Sci Monit Basic Res · 2018 Jan · PMID 29307883 · Full text
BACKGROUND Sodium glucose transporter-2 inhibitors are the newest antidiabetic drugs that seem to be cardioprotective and can prevent type 2 diabetes in patients with high cardiovascular risks. Previous clinical trials h...
BACKGROUND Sodium glucose transporter-2 inhibitors are the newest antidiabetic drugs that seem to be cardioprotective and can prevent type 2 diabetes in patients with high cardiovascular risks. Previous clinical trials have shown that these inhibitors can alleviate endothelial dysfunction, but the mechanism of action remains unknown. How SGLT inhibitor influences the release of NO in PA-induced HUVECs has never been reported. MATERIAL AND METHODS To explore the potential effects of the endothelial-protective mechanism of phlorizin and its impact on nitric oxide (NO), human umbilical vein endothelial cells (HUVECs) were incubated with palmitic acid (PA) and then treated with phlorizin. Western blotting was performed to assess the phosphorylation of AKT, eNOS, and IRS-1. To further explore potential targets, siRNA transfection was used to demonstrate the role of SGLT1 and SGLT2. RESULTS Phlorizin suppressed the expression of SGLT1 and SGLT2, activated the PI3K/AKT/eNOS signaling pathway, increased the output of NO, and promoted the consumption of glucose in PA-induced HUVECs. Through demonstrating siRNA suppression of the expression of SGLT1 and SGLT2 in PA-induced HUVECs, this study provides a new understanding of the mechanism behind SGLT1 and SGLT2. CONCLUSIONS Our data demonstrate that phlorizin ameliorates the endothelial dysfunction link with the activation of the PI3K/AKT/eNOS signaling pathway and augmentation of the release of NO, partially through suppressing the expression of SGLT1 and SGLT2 in PA-induced HUVECS.
Alternate-Nostril Yoga Breathing Reduced Blood Pressure While Increasing Performance in a Vigilance Test.
Telles S, Verma S, Sharma SK … +2 more , Gupta RK, Balkrishna A
Med Sci Monit Basic Res · 2017 Dec · PMID 29284770 · Full text
BACKGROUND Reports suggest that vigilance or sustained attention increases sympathetic activity. A persistent increase in sympathetic activity can lead to an increase in blood pressure. Alternate-nostril yoga breathing h...
BACKGROUND Reports suggest that vigilance or sustained attention increases sympathetic activity. A persistent increase in sympathetic activity can lead to an increase in blood pressure. Alternate-nostril yoga breathing has been shown to be useful to (i) improve attention and (ii) decrease the systolic and diastolic blood pressure. Earlier studies did not report simultaneous recordings of the blood pressure and performance in vigilance tests after alternate-nostril yoga breathing. With this background, the present study was planned to determine if 15 minutes of alternate nostril yoga breathing could improve the performance in a vigilance test without an increase in blood pressure. MATERIAL AND METHODS Fifteen healthy male volunteers participated in the study (group mean age ±SD, 22.4±2.4 years). Participants were assessed on 3 separate days in 3 different sessions. These were (i) alternate nostril yoga breathing, (ii) breath awareness, and (iii) sitting quietly as a control. Blood pressure and the digit vigilance test were simultaneously assessed before and after each session. RESULTS Systolic blood pressure (p<0.01), mean arterial blood pressure (p<0.05), and the time taken to complete the digit vigilance test (p<0.05) significantly decreased following alternate-nostril yoga breathing. The time taken to complete the digit vigilance test differed significantly between sessions (p<0.05). The time taken to complete the digit vigilance test was also significantly decreased after sitting quietly (p<0.01). CONCLUSIONS Alternate-nostril yoga breathing appears to improve performance in the digit vigilance test, along with a reduction in systolic blood pressure. This is suggestive of better vigilance without sympathetic activation.
Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet.
Goncalves GK, Caldeira de Oliveira TH, de Oliveira Belo N
Med Sci Monit Basic Res · 2017 Dec · PMID 29249795 · Full text
BACKGROUND Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims...
BACKGROUND Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. MATERIAL AND METHODS Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. RESULTS A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. CONCLUSIONS The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model.
Effects of Nicotine and Tocotrienol-Rich Fraction Supplementation on Cytoskeletal Structures of Murine Pre-Implantation Embryos.
Hamirah NK, Kamsani YS, Mohamed Nor Khan NA … +2 more , Ab Rahim S, Rajikin MH
Med Sci Monit Basic Res · 2017 Dec · PMID 29217815 · Full text
BACKGROUND Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. The objective of this study was to evaluate the effects of nicotine, which is a source...
BACKGROUND Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. The objective of this study was to evaluate the effects of nicotine, which is a source of oxidative stress, and subsequent supplementation with Tocotrienol-rich fraction (TRF) on actin and tubulin of 2- and 8-cell murine embryos. MATERIAL AND METHODS Thirty female Balb/C mice were divided into 4 groups: Group 1 received: subcutaneous (sc) injection of 0.9% NaCl; Group 2 received sc injection of 3.0 nicotine mg/kg bw/day; Group 3 received 3.0 sc injection of nicotine mg/kg bw/day +60 mg/kg bw/day TRF; and Group 4 received 60 sc injection of TRF mg/kg bw/day for 7 consecutive days. The animals were superovulated with 5 IU PMSG followed by 5 IU hCG 48 h later. Animals were cohabited with fertile males overnight and euthanized through cervical dislocation at 24 h post coitum. Embryos at the 2- and 8-cell stages were harvested, fixed, and stained to visualize actin and tubulin distributions by using CLSM. RESULTS Results showed that at 2-cell stage, actin intensities were significantly reduced in the nicotine group compared to that of the control group (p<0.001). In Group 3, the intensity of actin significantly increased compared to that of the nicotine group (p<0.001). At 8-cell stage, actin intensity of the nicotine group was significantly lower than that of the control group (p<0.001). The intensities of actin in Group 3 were increased compared to that of nicotine treatment alone (p<0.001). The same trend was seen in tubulin at 2- and 8-cell stages. Interestingly, both actin and tubulin structures in the TRF-treated groups were enhanced compared to the control. CONCLUSIONS This study suggests that TRF prevents the deleterious effects of nicotine on the cytoskeletal structures of 2- and 8-cell stages of pre-implantation mice embryos in vitro.
Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation.
Abou-Hamdan M, Gharib B, Bajenoff M … +2 more , Julia V, de Reggi M
Med Sci Monit Basic Res · 2017 Nov · PMID 29176546 · Full text
BACKGROUND Migration of leukocytes into airways is the hallmark of allergic asthma. The aim of this study was to target the pathological process using pantethine, a pleiotropic natural compound which has been recently sh...
BACKGROUND Migration of leukocytes into airways is the hallmark of allergic asthma. The aim of this study was to target the pathological process using pantethine, a pleiotropic natural compound which has been recently shown to down-regulate chemokine-driven T cell migration. MATERIAL AND METHODS Mice were sensitized to the Leishmania LACK antigen, then treated or not treated with pantethine and exposed to LACK or saline aerosol. After sacrifice of the animals, cells in the bronchoalveolar lavage were analyzed and inflammatory parameters were determined to evaluate inflammation seriousness. RESULTS As compared to untreated animals, pantethine-treated animals displayed a moderated response to the allergen, as documented by decreased infiltration of inflammatory cells (all types), in addition to reduced levels of lung Th2 cytokines and circulating LACK-specific IgE. CONCLUSIONS These data reveal the potential therapeutic importance of pantethine to moderate allergic asthma pathology. The compound has been previously shown to exert a broad range of protective activity in animals and in humans, with few or no adverse effects.
Immune-Neuroendocrine Interactions: Evolution, Ecology, and Susceptibility to Illness.
Blom JMC, Ottaviani E
Med Sci Monit Basic Res · 2017 Nov · PMID 29142191 · Full text
The integration between immune and neuroendocrine systems is crucial for maintaining homeostasis from invertebrates to humans. In the first, the phagocytic cell, i.e., the immunocyte, is the main actor, while in the latt...
The integration between immune and neuroendocrine systems is crucial for maintaining homeostasis from invertebrates to humans. In the first, the phagocytic cell, i.e., the immunocyte, is the main actor, while in the latter, the principle player is the lymphocyte. Immunocytes are characterized by the presence of pro-opiomelanocortin (POMC) peptides, CRH, and other molecules that display a significant similarity to their mammalian counterparts regarding their functions, as both are mainly involved in fundamental functions such as immune (chemotaxis, phagocytosis, cytotoxicity, etc.) and neuroendocrine (stress) responses. Furthermore, the immune-neuroendocrine system provides vital answers to ecological and immunological demands in terms of economy and efficiency. Finally, susceptibility to disease emerges as the result of a continuous dynamic interaction between the world within and the world outside. New fields such as ecological immunology study the susceptibility to pathogens in an evolutionary perspective while the field of neuro-endocrine-immunology studies the susceptibility from a more immediate perspective.
Identification of 2 Novel Mutations in ATP2C1 Gene in Hailey-Hailey Disease and a Literature Review of Variations in a Chinese Han Population.
Xu K, Shi B, Diao Q … +2 more , Jiang X, Xiao Y
Med Sci Monit Basic Res · 2017 Nov · PMID 29104283 · Full text
BACKGROUND Hailey-Hailey disease (HHD) is a rare autosomal dominant skin condition. The ATP2C1 gene was identified as the defective gene in HHD. To date, 166 pathogenic mutations in ATP2C1 have been observed worldwide. T...
BACKGROUND Hailey-Hailey disease (HHD) is a rare autosomal dominant skin condition. The ATP2C1 gene was identified as the defective gene in HHD. To date, 166 pathogenic mutations in ATP2C1 have been observed worldwide. The aim of this study was to identify variations in HHD and summarize the features of the mutations identified in China. MATERIAL AND METHODS We examined 2 familial and 2 sporadic cases of HHD. Genomic DNA polymerase chain reaction and direct sequencing of the ATP2C1 were performed from HHD patients, unaffected family members, and 200 healthy individuals. We also searched the published literature for data about the ATP2C1 gene using PubMed and the Chinese Biological Medicine Database. RESULTS We detected 3 heterozygous mutations, including 2 novel frameshift mutations (c.819insA (273LfsX) and c.1264insTAGATGG (421LfsX)) and 1 recurrent nonsense mutation (c.115C>T (R39X)). To the best of our knowledge, 90 different mutations (including our current results) have been reported in China, all of which occurred in the Chinese Han population. CONCLUSIONS Our data may add to the existing list of ATP2C1 mutations and provide new insight into genetic variants of HHD in China.
Tissue Engineered Small Vessel Conduits - The Anti-Thrombotic Effect of Re-Endothelialization of Decellularized Baboon Arteries: A Preliminary Experimental Study.
Meiring M, Khemisi M, Laker L … +2 more , Dohmen PM, Smit FE
Med Sci Monit Basic Res · 2017 Oct · PMID 29081492 · Full text
BACKGROUND The use of decellularized biological scaffolds for the reconstruction of small-diameter vascular grafts remains a challenge in tissue engineering. Thrombogenicity is an important cause of obstruction in these...
BACKGROUND The use of decellularized biological scaffolds for the reconstruction of small-diameter vascular grafts remains a challenge in tissue engineering. Thrombogenicity is an important cause of obstruction in these vessels due to decellularization. Seeding of the decellularized vascular constructs with endothelial cells is therefore a prerequisite for the prevention of thrombosis. The aim of this study was to seed decellularized baboon arteries with endothelial cells and to compare the thrombogenicity to that of decellularized arteries after circulation of blood. MATERIAL AND METHODS Carotid, radial, and femoral arteries (12 arteries in total) were harvested from 2 Papio ursinus baboons. Ten arteries were decellularized. Normal morphology was confirmed in the control vessels. The effect of re-endothelialization was studied in the vessel scaffolds using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Decellularization resulted in vessel scaffolds with well-preserved extracellular matrix and intact basal membranes. Six of the decellularized vessel scaffolds were seeded with viable human umbilical vein endothelial cells (HUVEC). Luminal endothelialization was established after 7 days in a bioreactor and SEM confirmed confluency. Two control, 4 decellularized, and 6 decellularized re-endothelialized vessel scaffolds were studied in an in vitro flow chamber using baboon blood. RESULTS The decellularized arteries showed an absence of endothelial lining, and an intact basement membrane. The seeding process produced a complete endothelial layer on the surfaces of the arteries. After perfusion with whole blood, no thrombi were formed in the control arteries and re-endothelialized vessels. Widespread platelet activation and adhesion occurred in the decellularized vessels despite a relatively intact basal membrane. CONCLUSIONS This study supports the development of re-endothelialized tissue engineered small-vessel conduits.
A Retrospective Chart Analysis with Follow-Up of Cogmed Working Memory Training in Children and Adolescents with Autism Spectrum Disorder.
Weckstein SM, Weckstein EJ, Parker CD … +1 more , Westerman MW
Med Sci Monit Basic Res · 2017 Oct · PMID 29033450 · Full text
BACKGROUND This case study was undertaken in an effort to assess whether children/adolescents with Autism Spectrum Disorder (ASD) experience improvement in comorbid ADHD following Cogmed Working Memory Training (CWMT). T...
BACKGROUND This case study was undertaken in an effort to assess whether children/adolescents with Autism Spectrum Disorder (ASD) experience improvement in comorbid ADHD following Cogmed Working Memory Training (CWMT). This treatment intervention has been shown to improve ADHD symptoms in children and adolescents; however, there have been no studies on its use with individuals with ASD. MATERIAL AND METHODS CWMT is a computer-based program that consists of 13 auditory, visual, visual spatial, and combined exercises that are practiced for 45 minutes a day, 5 days a week, for 5 weeks. Fifteen children/adolescents between the ages of 9 and 19 years with ASD and comorbid ADHD undertook a trial of CWMT. A 1-month follow-up and 2 longitudinal follow-ups were implemented. RESULTS The retrospective chart analysis and follow-up demonstrated improvement in attention and focus, impulsivity, emotional reactivity, and academic achievement in individuals with ASD and comorbid ADHD. Those benefits remained the same or increased over time. A number of participants also had benefits in their social interaction/social awareness. CONCLUSIONS CWMT has the potential to be an effective treatment intervention for children and adolescents with ASD because of its benign computer-based nature that seems to engage the unique learning style of this population. The authors hope that this paper will encourage others to study the ability of CWMT to be utilized in improving ADHD symptoms as well as social interaction/social awareness in individuals with ASD.
A New Clinically Relevant T-Score Standard to Interpret Bone Status in a Sheep Model.
Heiss C, Kern S, Malhan D … +11 more , Böcker W, Engelhardt M, Daghma DES, Stoetzel S, Schmitt J, Ivo M, Kauschke V, Lips KS, Tushtev K, Rezwan K, El Khassawna T
Med Sci Monit Basic Res · 2017 Oct · PMID 28966340 · Full text
BACKGROUND Osteoporosis is diagnosed by bone loss using a radiological parameter called T-score. Preclinical studies use DXA to evaluate bone status were the T-score is referenced on bone mineral density (BMD) values of...
BACKGROUND Osteoporosis is diagnosed by bone loss using a radiological parameter called T-score. Preclinical studies use DXA to evaluate bone status were the T-score is referenced on bone mineral density (BMD) values of the same animals before treatment. Clinically, the reference BMD represents values of an independent group of healthy patients around 30 years old. The present study established a clinically similar T-score standard to diagnose osteoporosis in a sheep model. MATERIAL AND METHODS We used 31 female merino land sheep (average 5.5 years old) to study osteoporosis. The following groups were compared using DXA measurement: 1) control; 2) ovariectomized (OVX); 3) OVX combined with a deficient diet (OVXD); and 4) OVXD combined with methylprednisolone administration (OVXDS). Further, an independent group of 32 healthy sheep (4-6 years old) were measured as an independent baseline. BMD was measured at 0 months, 3 months, and 8 months after treatment. RESULTS The same significance pattern between the treated groups and either baseline groups was seen. However, using an independent baseline changed the "clinical" interpretation of the data from an osteoporotic bone status (T-score <-2.5) after 3 months of OXDS treatment into an osteopenic bone status (T-score <-1.5 to -2.4). CONCLUSIONS Using an independent baseline enhanced the statistical significance and showed the clinical relevance. Furthermore, an independent baseline is a reliable alternative to use of a new control group for future experiments and thus reduces the number of animals needed by eliminating the need for a control and corresponding to clinical practice.
Chemical Composition and Antioxidant, Anti-Inflammatory, and Antiproliferative Activities of Lebanese Ephedra Campylopoda Plant.
Kallassy H, Fayyad-Kazan M, Makki R … +7 more , El-Makhour Y, Rammal H, Leger DY, Sol V, Fayyad-Kazan H, Liagre B, Badran B
Med Sci Monit Basic Res · 2017 Sep · PMID 28947729 · Full text
BACKGROUND: This study aimed to identify the phytochemical content and evaluate the antioxidant, anti-inflammatory, and antiproliferative capacities of various solvent extracts of stems. MATERIAL/METHODS: Fresh stems we...
BACKGROUND: This study aimed to identify the phytochemical content and evaluate the antioxidant, anti-inflammatory, and antiproliferative capacities of various solvent extracts of stems. MATERIAL/METHODS: Fresh stems were suspended in 3 different solvent systems, including distilled water, ethanol, and methanol The chemical composition was determined using high-performance liquid chromatography (HPLC), and the content of essential oil of this plant species was determined by gas chromatography (GC) coupled with mass spectrometry (MS). Antioxidant activity was determined using DPPH radical scavenging and Fe-chelating activity assays. Anti-inflammatory capacity was estimated by both evaluating RAW 264.7 murine macrophage cells-mediated secretion of PGE using ELISA technique, and quantifying the mRNA level of the pro-inflammatory cytokines (IL-α, IL-β and IL-6), chemokines (CCL3 and CCL4), and inflammation-inducible COX-2 and iNOS enzymes using quantitative real-time PCR (qRT-PCR). The antiproliferative potential was determined using the XTT viability assay. RESULTS: Our results showed that the alcoholic extracts were better than the aqueous one in terms of their chemical composition. In parallel, the alcoholic extracts showed more potent antioxidant, anti-inflammatory, and antiproliferative capacities than aqueous extract. CONCLUSIONS: Our observations suggest that Ephedra campylopoda plant could be a promising resource of natural products with antioxidant, anti-inflammatory and antiproliferative capacities.
Targeting Overexpressed Activating Transcription Factor 1 (ATF1) Inhibits Proliferation and Migration and Enhances Sensitivity to Paclitaxel In Esophageal Cancer Cells.
Hao Q, Zhao X, Zhang Y … +3 more , Dong Z, Hu T, Chen P
Med Sci Monit Basic Res · 2017 Sep · PMID 28912415 · Full text
BACKGROUND: Previous reports showed that Activating Transcription Factor 1 (ATF1) plays an important role in tumor progression in a tumor-specific manner. However, little is known about the expression and role of ATF1 in...
BACKGROUND: Previous reports showed that Activating Transcription Factor 1 (ATF1) plays an important role in tumor progression in a tumor-specific manner. However, little is known about the expression and role of ATF1 in esophageal cancer. MATERIAL/METHODS: The expression of ATF1 was examined by immunohistochemistry and Western blotting. The correlation between the expression of ATF1 and clinical characteristics of esophageal squamous cell carcinomas (ESCC) patients was analyzed by Fisher’s exact test. The role of cell proliferation, clonogenic survival, migration, and invasion , as well as the sensitization to paclitaxel, were determined after knockdown of ATF1 by siRNA. RESULTS: ATF1 was overexpressed in ESCC tissues, which was positively correlated with lymph node metastasis, poor differentiation, and early tumor invasion of esophageal cancer patients. Knockdown of ATF1 effectively reduced cell proliferation, induced S phase cell cycle arrest, and inhibited cell migration and invasion. Moreover, silencing of ATF1 significantly enhanced the sensitivity of esophageal cancer cells to paclitaxel. CONCLUSIONS: These findings suggest that ATF1 is a promising drug target for esophageal cancer.
A Retrospective Study: The Significance of Combined Testing of Serum Markers for Diagnosis of Rheumatoid Arthritis.
Mu F, Wu H, Wang Y
Med Sci Monit Basic Res · 2017 Aug · PMID 28855496 · Full text
BACKGROUND There have been few studies on the value of various antibody combinations in rheumatoid arthritis (RA) diagnosis, and a lack of studies with large sample sizes, especially in the Chinese population. This study...
BACKGROUND There have been few studies on the value of various antibody combinations in rheumatoid arthritis (RA) diagnosis, and a lack of studies with large sample sizes, especially in the Chinese population. This study retrospectively evaluated the diagnostic value of a combined assay of five auto-antibodies [anti-cyclic citrullinated peptide (anti-CCP), anti-keratin (AKA), anti-RA 33, glucose-6-phosphate isomerase (GPI), and rheumatoid factor (RF)] for RA. MATERIAL AND METHODS Data were obtained from 5,725 patients with rheumatic diseases in Southwest Hospital of Chongqing from 2011 to 2014. Detection of the five serological markers was performed for all study patients using the appropriate method for each antibody. RESULTS It was found that of the 5,725 patients, the positive rates for RF, anti-CCP, anti-RA 33, AKA, and GPI were 52.5%, 40.1%, 12.8%, 12.0%, and 50.0% respectively. In RA patients, the positive rates were 83.3%, 68.5%, 16.6%, 20.8%, and 77.9% respectively, which were all significantly higher than those detected in patients with the other diseases (p<0.01). The areas under the receiver operator characteristic (ROC) curve for RF, anti-CCP, anti-RA 33, AKA, and GPI were 0.857, 0.831, 0.528, 0.602, and 0.822 respectively, indicating that these five serological markers display favorable diagnostic value for RA. There were positive correlations between anti-CCP antibody and RF and GPI (p<0.01) and between RF and GPI (p<0.01), but no correlation between anti-RA 33 and AKA (p<0.01). The specificity of the combination of anti-CCP, AKA, and GPI was 100% for RA diagnosis. CONCLUSIONS The combined assay of serological markers significantly improved the diagnostic specificity for RA. The diagnostic value of RF for RA was the highest and the combined assay for anti-CCP, AKA, and GPI had the highest specificity for RA diagnosis.
Reprogramming Bone Marrow Stem Cells to Functional Endothelial Cells in a Mini Pig Animal Model.
Schlegel F, Appler M, Halling M … +4 more , Smit FE, Mohr FW, Dhein S, Dohmen PM
Med Sci Monit Basic Res · 2017 Aug · PMID 28814711 · Full text
BACKGROUND The aims of this study were to compare the morphological, biochemical, and functional properties of reprogrammed bone marrow stem cell (BMSC)-derived arterial endothelial cells (AECs) and venous endothelial ce...
BACKGROUND The aims of this study were to compare the morphological, biochemical, and functional properties of reprogrammed bone marrow stem cell (BMSC)-derived arterial endothelial cells (AECs) and venous endothelial cells (VECs), following adenosine triphosphate (ATP)-stimulation in a mini pig animal model. MATERIAL AND METHODS Bone marrow aspiration was performed in six adult mini pigs. Harvested mononuclear cells were isolated, cultured, and treated with vascular endothelial growth factor (VEGF) (16 µg/ml). Transformed cells were characterized using immunofluorescence staining for CD31 and von Willebrandt factor (vWF) and expression of endothelial nitric oxide synthase (eNOS). Cell release of nitric oxide (cNO) was measured using spectrophotometry. Matrigel assays were used to investigate angiogenesis in transformed BMSCs. RESULTS Reprogrammed BMSCs in culture showed a typical cobblestone-like pattern of growth. Immunofluorescence staining was positive for CD31 and vWF expression. Expression of eNOS, using immunofluorescence staining and Western blot, showed no difference between the reprogrammed BMSCs and VECs. Spectrophotometric examination following stimulation with 10mmol/l ATP, showed comparable cNO release for reprogrammed BMSCs (10.87±1.76 pmol/106 cells/min) and VECs (13.23±2.16 pmol/10^6 cells/min), but reduced cNO release for AECS (3.44±0.75 pmol/10^6 cells/min). Matrigel assay for angiogenesis showed vascular tube formation of differentiated BMSC endothelial cells (grade 3.25). BMSCs cultured without VEGF did not demonstrate vascular tube formation. CONCLUSIONS The findings of this study showed that eNOS expression and release of NO could be used to show that BMSCs can be reprogrammed to functional VECs and AECs.
Chemical Composition, Antioxidant, Anti-Inflammatory, and Antiproliferative Activities of the Plant Lebanese Crataegus Azarolus L.
Kallassy H, Fayyad-Kazan M, Makki R … +8 more , El-Makhour Y, Hamade E, Rammal H, Leger DY, Sol V, Fayyad-Kazan H, Liagre B, Badran B
Med Sci Monit Basic Res · 2017 Aug · PMID 28769026 · Full text
BACKGROUND In the present study, phytochemical screening, antioxidant, anti-inflammatory, and antiproliferative capacities of 3 extracts from leaves of Lebanese Crataegus azarolus L. were evaluated. MATERIAL AND METHODS...
BACKGROUND In the present study, phytochemical screening, antioxidant, anti-inflammatory, and antiproliferative capacities of 3 extracts from leaves of Lebanese Crataegus azarolus L. were evaluated. MATERIAL AND METHODS Fresh leaves were dissolved in 3 different solvents: distilled water, ethanol, and methanol. The chemical composition was determined using high-performance liquid chromatography (HPLC) and the content of essential oil of this plant was examined by gas chromatography (GC) coupled with mass spectrometry (MS). The antioxidant potential was evaluated using DPPH radical scavenging and Fe2+ chelating activity assays. Anti-inflammatory effect was investigated by measuring the secreted amounts of the proinflammatory mediator PGE2 using ELISA technique, as well as by assaying the mRNA levels of the proinflammatory cytokines (IL-α, IL-β, and Il-6), chemokines (CCL3 and CCL4) and inflammation-sensitive COX2 and iNOS enzymes using quantitative real-time PCR (qRT-PCR). The antiproliferative effect was evaluated using the XTT viability assay. RESULTS The obtained results show that alcohol (methanol and ethanol) extracts were rich in bioactive molecules with medical relevance and exerted substantial antioxidant, anti-inflammatory, and antiproliferative capacities. On the other hand, aqueous extract contained fewer chemical components and exhibited less therapeutic efficiency. CONCLUSIONS Our observations indicate that Crataegus azarolus L. could be used for treating diseases related to oxidative stress, inflammatory reactions, and uncontrolled cell growth.
Comparison of Commercially Available Blood Collection Tubes Containing Sodium Citrate and Hirudin in Platelet Aggregation Testing.
Janse van Rensburg WJ, van der Merwe P
Med Sci Monit Basic Res · 2017 Jul · PMID 28747619 · Full text
BACKGROUND Platelet reactivity assessment is an important tool in both the causal determination of bleeding diathesis as well as in the evaluation of the efficacy of anti-platelet therapy in patients at risk of thrombosi...
BACKGROUND Platelet reactivity assessment is an important tool in both the causal determination of bleeding diathesis as well as in the evaluation of the efficacy of anti-platelet therapy in patients at risk of thrombosis. Sodium citrate is the most widely used anticoagulant for hemostasis investigations. However, some doubt exists over the suitability of sodium citrate in platelet function testing. Hirudin has been suggested as a superior replacement. Nevertheless, only 1 study compared citrated and hirudin treated samples with light transmission aggregometry. Therefore, limited evidence exists to conclusively prove the supremacy of hirudin over sodium citrate in light transmission aggregometry. The aim of our study was to compare citrated and hirudin treated samples, collected in commercially available blood collection tubes, using the 5 most common agonists, with light transmission aggregometry. MATERIAL AND METHODS Blood was obtained from 20 healthy volunteers. Platelet counts were performed on platelet-rich plasma. Light transmission aggregometry was performed within 4 h of sample collection using ADP, collagen, arachidonic acid, epinephrine, and ristocetin as agonists. RESULTS Platelet counts for the respective anticoagulants did not differ significantly. ADP-induced aggregation was comparable between the samples. However, among all the agonists, hirudin-treated platelets had significantly weaker aggregatory responses. CONCLUSIONS Commercially available sodium citrate should remain the anticoagulant of choice for routine platelet function testing in our setting. However, the time limitation associated with the use of sodium citrate in platelet function testing remains a concern. Thus, alternative anticoagulants should still be explored.
Surgery for Cardiac Papillary Fibroelastoma: A 12-Year Single Institution Experience.
Mkalaluh S, Szczechowicz M, Torabi S … +5 more , Dib B, Sabashnikov A, Mashhour A, Karck M, Weymann A
Med Sci Monit Basic Res · 2017 Jul · PMID 28706178 · Full text
BACKGROUND We reviewed our clinical experience with cardiac papillary fibroelastoma from 2005 to 2017. The objective of this study was to investigate the clinical and operative data, as well as the early survival rate an...
BACKGROUND We reviewed our clinical experience with cardiac papillary fibroelastoma from 2005 to 2017. The objective of this study was to investigate the clinical and operative data, as well as the early survival rate and immediate postoperative complications. MATERIAL AND METHODS We performed a retrospective analysis of 11 patients (eight males and three females) who underwent resection of cardiac papillary fibroelastoma in our institution. RESULTS Mean age at tumor diagnosis was 60±14 years. The mean dimension of the tumor was 14±11 mm. The most common symptoms were dyspnea, palpitation, and angina pectoris, while one patient had recurrent fever attacks and another patient had a transient ischemic attack. Two patients had concomitant malignant tumors (cervical and colon carcinoma) and another two had concomitant benign neoplasms (liver cyst and thyroid adenoma). Bypass and cross clamp times were 77±32 minutes and 54±18 minutes, respectively. The tumors were found predominantly on cardiac valves (n=7). In eight cases, only tumor extirpation was performed, whereas in the other three cases, the valves had to be replaced. The mean intensive care unit length of stay was 1.1±0.3 days and there was no in-hospital mortality. All patients were alive at one-year follow-up and the survival rate was 91% in the mean follow-up period of 4.15 years. CONCLUSIONS The surgical treatment of cardiac papillary fibroelastoma was curative and safe. Thus, potential complications such as embolization or mechanical irritation of the valves can be avoided without high surgical risk.
Vascular Graft Impregnation with Antibiotics: The Influence of High Concentrations of Rifampin, Vancomycin, Daptomycin, and Bacteriophage Endolysin HY-133 on Viability of Vascular Cells.
Herten M, Idelevich EA, Sielker S … +5 more , Becker K, Scherzinger AS, Osada N, Torsello GB, Bisdas T
Med Sci Monit Basic Res · 2017 Jun · PMID 28652563 · Full text
BACKGROUND Rifampin-soaked synthetic prosthetic grafts have been widely used for prevention or treatment of vascular graft infections (VGIs). This in vitro study investigated the effect of the antibiotics daptomycin and...
BACKGROUND Rifampin-soaked synthetic prosthetic grafts have been widely used for prevention or treatment of vascular graft infections (VGIs). This in vitro study investigated the effect of the antibiotics daptomycin and vancomycin and the new recombinant bacteriophage endolysin HY-133 on vascular cells, as potential alternatives compared to rifampin. MATERIAL AND METHODS Primary human ECs, vascular smooth muscle cells (vSMC), and fibroblasts were cultivated in 96-well plates and incubated with rifampin, daptomycin, vancomycin, and endolysin HY-133 for 24 h. Subsequently, after washing, cell viability was determined by measuring mitochondrial ATP concentration. Antibiotics were used in their corresponding minimum and maximum serum concentrations, in decimal multiples and in maximum soaking concentration. The experiments were performed in triplicate. RESULTS The 10-fold max serum concentrations of rifampin, daptomycin, and vancomycin did not influence viability of EC and vSMC (100 µg/ml, p>0.170). Higher concentrations of rifampin (>1 mg/ml) significantly (p<0.001) reduced cell viability of all cell types. For the other antibiotics, high concentrations (close to maximum soaking concentration) were most cytotoxic for EC and vSMC and fibroblasts (p<0.001). Endolysin did not display any cytotoxicity towards vascular cells. CONCLUSIONS Results of this in vitro study show the high cytotoxicity of rifampin against vascular cells, and may re-initiate the discussion about the benefit of prophylactic pre-soaking in high concentrations of rifampin. Further studies are necessary to determine the influence of rifampin on the restoration of vessel functionality versus its prophylactic effect against VGIs. Future use of recombinant phage endolysins for alternative prophylactic strategies needs further investigations.
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