Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical implications of the SETBP1 mutation in patients with primary myelodysplastic syndrome and its stability during disease progression

Mutations of the SET binding protein 1 (SETBP1) gene have been identified in patients with myeloid neoplasms, but the clinical relevance of this mutation and its association with other gene mutations in myelodysplastic syndrome (MDS) and the stability during disease progression remains unclear. Mutations in SETBP1 gene at exon 4 were analyzed by polymerase chain reaction and direct sequencing in 430 MDS patients. The results were correlated with clinical features, cytogenetics, gene mutations and treatment outcomes. SETBP1 mutations were identified in 14 (3.3%) of the 430 patients with primary MDS based on the FAB classification and 8 (2.4%) of the 333 patients based on the WHO classification. The SETBP1 mutation was closely associated with higher white blood cell counts, isochromosome of 17q, monosomy 7, and mutations of ASXL1, EZH2 and SRSF2. With a median follow‐up of 43.9 months, MDS patients, based on either the FAB or WHO classification, had a significantly poorer overall survival (OS) if they harbored SETBP1 mutation. Further, SETBP1 mutation was an independent poor prognostic factor for OS (HR = 1.842, CI 95%, 1.1018–3.332, P = 0.043) irrespective of age, sex, and the International Prognostic Scoring System. Sequential analysis showed that the original SETBP1 mutations in the eight SETBP1‐mutated patients studied were retained while two of the 101 SETBP1‐wild patients acquired novel SETBP1 mutations during follow‐ups. The SETBP1 mutation is associated with poor prognosis in MDS. The mutation can be acquired during the clinical course suggesting it may play a role in disease progression. Am. J. Hematol. 89:181–186, 2014. © 2013 Wiley Periodicals, Inc.
Association of Apolipoprotein E Genotype with Early Onset of Coronary Heart Disease in Greek Men

Apolipoprotein (apo) E polymorphism has been associated with coronary heart disease (CHD) although its relation to the age of CHD onset is still not defined. The age of onset of established CHD was obtained from 502 Greek men and compared to 103 healthy men. The age grouping was based on the age of CHD onset (earlier ≤44 years, n=73, intermediate 45-64 years, n=321, and later ≥65 years, n=108). Apo E genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the lipid profile was assessed. No differences in genotype and allele frequencies were found within the CHD groups. The apo ε3/4 genotype and the apo ε4 allele were less frequent in the earlier-onset group than in healthy men (11.0% vs 22.3%, Pearson Chi-Square p=0.028 and 6.8% vs 13.6%, Pearson Chi-Square p=0.023, respectively). The lipid profile was similar in all genotypes of all groups except for high-density lipoprotein cholesterol levels, which were higher in ε2 carriers compared to non-ε2 carriers (in mg/dL [±SD]; 44 [9] vs 39 [10], in mmol/L [±SD]; 1.1 [0.2] vs 1.0 [0.3] p=0.005). There is an association between apo E genotype and early onset of CHD in Greek men. In the earlier CHD onset group, the apo ε3/4 genotype was less frequent compared to healthy men. This supports that the apo ε3/4 genotype is associated with decreased risk of premature CHD. Because the results of similar studies are not consistent, it may be that the relationship between apo E genotype and CHD is related to ethnicity rather than a universal phenomenon.
HIV-1 reverse transcriptase connection subdomain mutations reduce template RNA degradation and enhance AZT excision

We previously proposed that mutations in the connection subdomain (cn) of HIV-1 reverse transcriptase increase AZT resistance by altering the balance between nucleotide excision and template RNA degradation. To test the predictions of this model, we analyzed the effects of previously identified cn mutations in combination with thymidine analog mutations (D67N, K70R, T215Y, and K219Q) on in vitro RNase H activity and AZT monophosphate (AZTMP) excision. We found that cn mutations G335C/D, N348I, A360I/V, V365I, and A376S decreased primary and secondary RNase H cleavages. The patient-derived cns increased ATP- and PPi-mediated AZTMP excision on an RNA template compared with a DNA template. One of 5 cns caused an increase in ATP-mediated AZTMP excision on a DNA template, whereas three cns showed a higher ratio of ATP- to PPi-mediated excision, indicating that some cn mutations also affect excision on a DNA substrate. Overall, the results strongly support the model that cn mutations increase AZT resistance by reducing template RNA degradation, thereby providing additional time for RT to excise AZTMP.
Reduction by Phytate-reduced Soybean β-Conglycinin of Plasma Triglyceride Level of Young and Adult Rats

This study examined the effects of soybean β-conglycinin, from which phytate was mostly removed, on the plasma lipids in young and adult rats. Male Wistar young (6 week-old) and adult (21 week-old) rats were fed high cholesterol diets containing 20% casein, soy protein isolate (SPI), or soybean β-conglycinin for 10 days. In young rats, although the food intake of the β-conglycinin group was higher than those of the casein and SPI groups, the weight gain was significantly lower than those of the other groups. However, in adult rats, the weight gain was not different among the groups. In young and adult rats, relative liver weights of SPI and β-conglycinin groups were significantly lower than that of the casein group, and the degree of the reduction was more marked in the β-conglycinin group than in the SPI group. In young rats, the plasma triglyceride level was significantly lower in the SPI and β-conglycinin groups than that in the casein group. In addition, the plasma triglyceride level of the β-conglycinin group was significantly lower than that of the SPI group. Plasma total cholesterol levels of the SPI and β-conglycinin groups were significantly lower than that of the casein group. However, there was little difference in the lowering effect between SPI and β-conglycinin. These results indicate that soybean β-conglycinin may have lowering functions not only on plasma total cholesterol level, but aiso on plasma triglyceride level.
Ghrelin induces cell migration through GHS‐R, CaMKII, AMPK, and NF‐κB signaling pathway in glioma cells

Ghrelin is a newly discovered gastric peptide which stimulates food intake, energy balance, and growth hormone release. Recent reports have also shown that circulating ghrelin can efficiently reach the brain. However, the molecular mechanisms and pathophysiologic roles underlying ghrelin‐induced glioma migration remain unclear. Glioma is the most common primary adult brain tumor with poor prognosis because of the spreading of tumor cell to the other regions of brain easily. In present study, we found that application of recombinant human ghrelin enhances the glioma cell migration in both rat C6 and human U251 cells. Ghrelin and its receptor GHS‐R (growth hormone secretagogue receptor) are expressed in a wide variety of tissues and cell types, including various cancer cells. However, little is known about the expression of ghrelin or GHS‐R in brain tumors. Here, we found that ghrelin increased GHS‐R receptor up‐regulation, and the enhancement of ghrelin‐induced glioma cell motility markedly inhibited by a GHS‐R antagonist. In addition, ghrelin‐mediated migration was attenuated by treatment of CaMKII inhibitor, and AMPK inhibitors and pre‐transfection with AMPK siRNA. Moreover, ghrelin stimulation also increased the phosphorylation of CaMKII and AMPK. Treatment with three different types of NF‐κB inhibitors or pre‐transfection with KM‐IKKα, or KM‐IKKβ also reduced ghrelin‐induced glioma cell migration. Moreover, treatment of ghrelin also induced IKKα/β activation, IκBα phosphorylation, p65 phosphorylation at Ser536, and increased NF‐κB‐DNA binding activity and κB‐transcriptional activity. These results indicate that ghrelin enhances migration of glioma cells is mainly regulated by the GHS‐R, CaMKII, AMPK, and NF‐κB pathway. J. Cell. Biochem. 112: 2931–2941, 2011. © 2011 Wiley‐Liss, Inc.
Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern

In order to investigate the associations between fatigue and depression, disability, and disease subtype, 207 individuals with clinically definite Multiple Sclerosis (MS) were administered the Fatigue Severity Scale and the Zung Self-rating Depression Scale during a regular clinic appointment. Their current level of disability was established using the Expanded Disability Status Scale. Fatigue and depression were highly correlated (r=0.58) even when the depression measure was corrected for items overlapping with fatigue and other symptoms or consequences of MS (r=0.44). Fatigue and disability were also correlated (r=0.33). Multiple regression revealed that both depressed mood and disability were significant predictors of fatigue, together accounting for approximately 23% of the variance in patient' self-reported fatigue. The combined groups of primary progressive (n=45) and secondary progressive patient (n=25) appeared to have higher fatigue scores than relapsing-remitting patient (n=137). However an analysis of covariance revealed that this apparent difference was in fact attributable almost exclusively to differences in disability among the three subtypes of MS. Other reports of differences in fatigue between subtypes of MS should be re-examined in light of this finding.
The significance of fatigue in relatives of palliative patients

Abstract Objective: The aim of this study was to explore the significance of fatigue among relatives of palliative patients. Method: This pilot study has a descriptive and cross-sectional design and is the report of four open-ended questions focusing on the relatives' experiences of fatigue. The study population consisted of relatives of patients who were cared for in palliative care settings either at home or in an institution in Uppsala County during a specific day. Results: The relatives were very tired and identified worries, uncertainty, the patient's suffering, and many demands as the causes for the fatigue. The most obvious consequences of the tiredness were a lack of motivation, feelings of insufficiency and apathy, and putting their own interests aside. Many relatives expressed that having the company of close family members, taking exercise and spending time outdoors gave them strength to carry on. The health care system could make the situation easier for relatives of patients in palliative care by providing good care for the patient, and psychosocial support and respite care for the relatives. Significance of results: The result of the pilot study is only preliminary, but it showed that relatives caring for patients in a late palliative phase suffer from great fatigue and require more attention, both scientifically and in the clinical settings.
Physicochemical, microstructural, and antibacterial properties of β-chitosan and kudzu starch composite films.

UNLABELLED This study investigated physicochemical, microstructural, and antibacterial properties of β-chitosan-kudzu starch composite films with addition of 0%, 20%, 60%, or 100% kudzu starch (w starch/w chitosan) in 1% chitosan solution. Molecular interactions between chitosan and kudzu starch and the crystal structure of the films were also determined. Adding 60% kudzu starch reduced water vapor permeability and solubility of pure β-chitosan film by about 15% and 20%, respectively, whereas mechanical strength and flexibility of the film were increased about 50% and 25%, respectively. Micrograph showed that β-chitosan film was totally amorphous, and the composite films generally became rougher with more starch added. Fourier transform infrared and X-ray diffraction spectra showed that the 2 film-forming components were compatible with each other. Pure β-chitosan film resulted in 9.5 and 11.5 log CFU/mL reduction in Escherichia coli and Listeria innocua based on plate count method, respectively. Addition of kudzu starch reduced the antibacterial activity of film, but still achieved 8.3 and 10.3 log CFU/mL reduction in E. coli and L. innocua, respectively when kudzu starch to chitosan weight ratio was 1:1. Reduced antibacterial activity might attribute to the interaction of amino groups in β-chitosan with the hydroxyl groups in kudzu starch. This study demonstrated that kudzu starch effectively improved water barrier of β-chitosan film, and the composite films retained strong antibacterial ability. PRACTICAL APPLICATION One percent of β-chitosan containing 60% kudzu starch (w/w chitosan) composite films possessed better mechanical and water barrier properties than pure β-chitosan films, and showed strong antibacterial activity against both Gram-positive and Gram-negative bacteria. The films may be used as wraps or coatings to prolong the shelf life of different foods or other similar applications.
Sustained Weight Loss After Gastric Banding Revision for Pouch-Related Problems

Objective:To assess the impact of revisional surgery after laparoscopic adjustable gastric banding (LAGB) on weight loss at 12 and 24 months. Background:There is no uniform consensus as to the optimal procedure for patients requiring revision after LAGB. Few studies address the issue of weight loss after band salvage procedures, despite this being a critical factor in deciding which reoperative procedure to choose. Methods:A retrospective analysis was conducted of adult patients who underwent LAGB from January 1, 2001 to June 30, 2009 at a single institution. Patients who required revision for pouch-related problems including band slippage, pouch dilation, and hiatal hernia were studied. Demographic data, body mass index (BMI), percentage excess weight loss (% EWL), and operative details were recorded. Weights were recorded at 12 and 24 months after revision. These were compared with initial weight, weight before revision, and weight in patients who did not have a reoperation. Results:Of 3876 patients, 390 patients were included in analysis of weight outcomes after revision. The procedure-related mortality was 0%. Early (30-day) complications occurred in 0.5%, late complications (erosion) in 0.5%, and 29 patients (7.4%) required a second revision. For patients undergoing revision, the initial weight was 124.06 ± 21.28 kg and BMI was 44.80 ± 6.12 kg/m2. At reoperation, weight was 89.18 ± 20.51 kg, BMI was 32.25 ± 6.50 kg/m2 and, %EWL was 54.13 ± 21.80%. Twelve months postrevision, weight was 92.24 ± 20.22 kg, BMI was 33.32 ± 6.41 kg/m2, and %EWL was 48.81 ± 22.71%. Weight was 92.42 ± 19.91 kg, BMI was 33.53 ± 6.25 kg/m2, and %EWL was 47.50 ± 22.91% twenty-four months postrevision. Conclusions:Reoperation for pouch-related problems after LAGB is safe and effective. Weight loss is maintained after reoperation.
Endoscopic sphincterotomy-induced pancreatitis: increased risk associated with nondilated bile ducts and sphincter of Oddi dysfunction.

OBJECTIVE to evaluate the relationship between common bile duct diameter and the risk of sphincterotomy-induced pancreatitis. METHODS Two hundred and ten consecutive patients were prospectively investigated. Patients were divided into three groups according to the indication for sphincterotomy: Group I had common bile duct stones (n = 108), group II had sphincter of Oddi dysfunction (n = 48), and group III had sphincterotomy for other indications (n = 54) (i.e., stent, dilation). RESULTS There were 62 males and 148 females with a mean age of 60 yr (range 15-93 yr). Eleven of the 210 patients (5.2%) developed pancreatitis. Other sphincterotomy-induced complications were bleeding (n = 2), cholangitis (n = 2), retroperitoneal duodenal perforation (n = 1), and bile duct leakage (n = 1). The percentages of pancreatitis in groups I (3.7%), II (12.5%), and III (1.9%) were significantly different (p = 0.03). Patients with nondilated common bile ducts (< or = 10 mm) had more pancreatitis than patients with dilated common bile ducts (8.8% vs. 2.8%), but the difference was not significant (p = 0.07). However, when group III was excluded from the analysis, there was a significant difference in the percentage of pancreatitis between the patients with nondilated bile ducts and those patients with dilated bile ducts (13.1% vs. 2.2%, respectively; p < 0.01). Analysis for trend did not show a significant inverse relationship between bile duct diameter and the rate of sphincterotomy-induced pancreatitis. However, for all complications combined, the inverse relationship between bile duct diameter and rate of sphincterotomy-induced complications was significant: < or = 5 mm (23.1%), > 5-10 mm (13.8%), > 10-15 mm (3.2%), > 15 mm (2.4%) (p = 0.002). CONCLUSIONS Endoscopic sphincterotomy is more hazardous in patients with nondilated bile ducts and sphincter of Oddi dysfunction. Further studies are needed to determine whether pancreatic stenting reduces the risk of sphincterotomy-induced pancreatitis in those clinical settings.
Effects of epoxyeicosatrienoic acids on the cardiac sodium channels in isolated rat ventricular myocytes

1 Whole‐cell Na+ currents (holding potential, −80 mV; test potential, −30 mV) in rat myocytes were inhibited by 8,9‐epoxyeicosatrienoic acid (8,9‐EET) in a dose‐dependent manner with 22 ± 4 % inhibition at 0.5 μM, 48 ± 5 % at 1 μM, and 73 ± 5 % at 5 μM (mean ± s.e.m., n= 10, P < 0.05 for each dose vs. control). Similar results were obtained with 5,6‐, 11,12‐, and 14,15‐EETs, while 8,9‐dihydroxyeicosatrienoic acid (DHET) was 3‐fold less potent and arachidonic acid was 10‐ to 20‐fold less potent. 2 8,9‐EET produced a dose‐dependent, hyperpolarized shift in the steady‐state membrane potential at half‐maximum inactivation (V½), without changing the slope factor. 8,9‐EET had no effect on the steady‐state activation of Na+ currents. 3 Inhibition of Na+ currents by 8,9‐EET was use dependent, and channel recovery was slowed. The effects of 8,9‐EET were greater at depolarized potentials. 4 Single channel recordings showed 8,9‐EET did not change the conductance or the number of active Na+ channels, but markedly decreased the probability of Na+ channel opening. These results were associated with a decrease in the channel open time and an increase in the channel closed times. 5 Incubation of cultured cardiac myocytes with 1 μM [3H]8,9‐EET showed that 25 % of the radioactivity was taken up by the cells over a 2 h period, and most of the uptake was incorporated into phospholipids, principally phosphatidylcholine. Analysis of the medium after a 2 h incubation indicated that 86 % of the radioactivity remained as [3H]8,9‐EET while 13 % was converted into [3H]8,9‐DHET. After a 30 min incubation, 1–2 % of the [3H]8,9‐EET uptake by cells remained as unesterified EET. 6 These results demonstrate that cardiac cells have a high capacity to take up and metabolize 8,9‐EET. 8,9‐EET is a potent use‐ and voltage‐dependent inhibitor of the cardiac Na+ channels through modulation of the channel gating behaviour.
Recognition of the Murine Coronavirus Genomic RNA Packaging Signal Depends on the Second RNA-Binding Domain of the Nucleocapsid Protein

ABSTRACT The coronavirus nucleocapsid (N) protein forms a helical ribonucleoprotein with the viral positive-strand RNA genome and binds to the principal constituent of the virion envelope, the membrane (M) protein, to facilitate assembly and budding. Besides these structural roles, N protein associates with a component of the replicase-transcriptase complex, nonstructural protein 3, at a critical early stage of infection. N protein has also been proposed to participate in the replication and selective packaging of genomic RNA and the transcription and translation of subgenomic mRNA. Coronavirus N proteins contain two structurally distinct RNA-binding domains, an unusual characteristic among RNA viruses. To probe the functions of these domains in the N protein of the model coronavirus mouse hepatitis virus (MHV), we constructed mutants in which each RNA-binding domain was replaced by its counterpart from the N protein of severe acute respiratory syndrome coronavirus (SARS-CoV). Mapping of revertants of the resulting chimeric viruses provided evidence for extensive intramolecular interactions between the two RNA-binding domains. Through analysis of viral RNA that was packaged into virions we identified the second of the two RNA-binding domains as a principal determinant of MHV packaging signal recognition. As expected, the interaction of N protein with M protein was not affected in either of the chimeric viruses. Moreover, the SARS-CoV N substitutions did not alter the fidelity of leader-body junction formation during subgenomic mRNA synthesis. These results more clearly delineate the functions of N protein and establish a basis for further exploration of the mechanism of genomic RNA packaging. IMPORTANCE This work describes the interactions of the two RNA-binding domains of the nucleocapsid protein of a model coronavirus, mouse hepatitis virus. The main finding is that the second of the two domains plays an essential role in recognizing the RNA structure that allows the selective packaging of genomic RNA into assembled virions.
Human cytomegalovirus infection promotes the stemness of U251 glioma cells

Glioblastoma (GBM) are the most common and aggressive tumors of human brain. Recent studies showed that human cytomegalovirus (HCMV) can induce malignant transformation of tumor cells to maintain stemness. Transcription factor 5 (ATF5) is an anti‐apoptotic protein that is highly expressed in malignant glioma. The aim of this study is to investigate the effect of HCMV infection on the stem cell makers of U251 cells. U251 cells were infected by AD169 HCMV strain (MOI = 1). The expression of stem cell makers (CD133, NES, Notch1) in infected U251 cells were compared with the expression in uninfected U251 cell to see the difference between them. Then, the changes of cell proliferation activity and the expression level of Notch intracellular domain (NICD), Notch1, ATF5, and IE protein were detected in the infected cells, and the expressions of Notch1 and NICD were increased. Cell proliferation assay showed that HCMV infection significantly increased the proliferation. These cells could form tumor spheres in non‐adherent conditions. Consistent with these findings, the effect of silencing ATF5 on the proliferation of HCMV‐infected U251 cells was also examined. The result shows that short interfering RNA‐mediated ATF5 downregulation inhibited this process. These findings imply that HCMV infection may regulate ATF5 signaling pathway to increase cell malignant traits and maintain stemness. J. Med. Virol. 89:878–886, 2017. © 2016 Wiley Periodicals, Inc.