Miracle-dz/UniFAR-FTUs huggingface dataset:
CMAR_A_302423 4455..4462

Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, People’s Republic of China Objective: Epithelial ovarian cancer (EOC) is one of the leading causes of death worldwide. The aim of this study was to explore the prognostic significance of prolyl-4-hydroxylase α subunit 2 (P4HA2) in patients with EOC. Patients and Methods: A total of 217 clinical samples (EOC tissues, 167 cases; normal ovarian, 50 cases) were collected and pathologically confirmed using hematoxylin and eosin (H&E) staining. P4HA2 expression in clinical samples was stained by immunohistochemistry (IHC). Relationship between P4HA2 expression and clinicopathological characteristics of EOC patients were analyzed using chi-square test. The differential expression of targets was analyzed in Oncomine database. The prognostic value of P4HA2 was investigated in clinical EOC patients and Kaplan–Meier (KM) Plotter database. Results: IHC staining showed that P4HA2 was significantly up-regulated in EOC tissues, compared to the normal tissues. Two databases retrieved from Oncomine database further confirmed the up-regulation P4HA2 in EOC. Chi-square test demonstrated that P4HA2 expression was associated with clinical stage (p=0.036), tumor grade (p<0.001), and residual disease (p=0.022). Both in clinical samples and KM Plotter database, high P4HA2 expression was significantly associated with worse progression-free survival (PFS) and overall survival (OS). Cox’s proportional hazards regression analysis suggested that high P4HA2 expression were independent risk factors for the survival of EOC patients. Besides, we confirmed the positive correlation between P4HA2 and COL1A1 expression. Moreover, COL1A1 was found to be up-regulated in EOC and also associated with short PFS and OS. Conclusion: The present study preliminarily proved that P4HA2 expression was associated with clinical outcome in EOC patients. P4HA2 might be a prognostic factor for EOC progression, and has the potential to be a valuable therapeutic target for EOC.
Translocation of GSK-3β, a trigger of permeability transition, is kinase activity-dependent and mediated by interaction with VDAC2

Background: Glycogen synthase kinse-3β (GSK-3β) promotes mitochondrial permeability transition (MPT), a mechanism of cell necrosis. Results: Efficient GSK-3β translocation to mitochondria requires its kinase activity, N-terminal domain and interaction with VDAC2 protein. Conclusion: MPT can be suppressed by inhibiting mitochondrial transport of GSK-3β. Significance: A strategy for cell protection without modifying the physiological function of GSK-3β is proposed. ABSTRACT Glycogen synthase kinase-3β (GSK-3β) is a major positive regulator of the mitochondrial permeability transition pore (mPTP), a principle trigger of cell death, under the condition of oxidative stress. However, the mechanism by which cytosolic GSK-3β translocates to mitochondria, promoting mPTP opening, remains unclear. Here we addressed this issue by analyses of the effect of site-directed mutations in GSK-3β on mitochondrial translocation and protein-protein interactions upon oxidative stress. H9c2 cardiomyoblasts were transfected http://www.jbc. org/cgi/doi/10.1074/jbc.M114.563924 The latest version is at JBC Papers in Press. Published on September 3, 2014 as Manuscript M114.563924
Study of the (cid:2) – (cid:2) interaction with femtoscopy correlations in pp and p–Pb collisions at the LHC

This work presents new constraints on the existence and the binding energy of a possible (cid:2) – (cid:2) bound state, the H-dibaryon, derived from (cid:2) – (cid:2) femtoscopic measurements by the ALICE collaboration. The results are obtained from a new measurement using the femtoscopy technique in pp collisions at √ s = 13 TeV and p–Pb collisions at √ s NN = 5 . 02 TeV, combined with previously published results from pp collisions at √ s = 7 TeV. The (cid:2) – (cid:2) scattering parameter space, spanned by the inverse scattering length f − 1 0 and the effective range d 0 , is constrained by comparing the measured (cid:2) – (cid:2) correlation function with calculations obtained within the Lednický model. The data are compatible with hypernuclei results and lattice computations, both predicting a shallow attractive interaction, and permit to test different theoretical approaches describing the (cid:2) – (cid:2) interaction. The region in the ( f − 1 0 , d 0 ) plane which would accommodate a (cid:2) – (cid:2) bound state is substantially restricted compared to previous studies. The binding energy of the possible (cid:2) – (cid:2) bound state is estimated within an effective-range expansion approach and is found to be B (cid:2)(cid:2) = 3 . 2 + 1 . 6 − 2 . 4 (stat) + 1 . 8 − 1 . 0 (syst) MeV.
Inflammation in Aging Mice Leading to Attenuated Allergic Airway Remodeling and Th2 Cell Differentiation Impaired GATA3-Dependent Chromatin

Age-related changes in lymphocytes are most prominent in the T cell compartment. There have been substantial numbers of reports on T cell function in aged mice and humans, such as on the production of Th1 and Th2 cytokines, but the results show considerable variation and contradictions. In the present study, we used 8- to 12-mo-old aging mice and a well-established in vitro Th1/Th2 cell differentiation culture system to identify molecular defects in Th1/Th2 cell differentiation that can be detected in the relatively early stages of aging. The capability to differentiate into Th2 cells is reduced in aging mouse CD4 (cid:1) T cells. Decreased activation of the ERK MAPK cascade upon TCR stimulation, but normal intracellular-free calcium ion concentration mobilization and normal IL-4-induced STAT6 activation were observed in aging mouse CD4 (cid:1) T cells. In addition, reduced expression of GATA3 was detected in developing Th2 cells. Chromatin remodeling of the Th2 cytokine gene locus was found to be impaired. Th2-dependent allergic airway inﬂammation was milder in aging mice compared with in young adult mice. These results suggest that the levels of Th2 cell differentiation and resulting Th2-dependent immune responses, including allergic airway inﬂammation, decline during aging through defects in the activation of the ERK MAPK cascade, expression of GATA3 protein and GATA3-dependent chromatin remodeling of the Th2 cytokine gene locus. In the present study, we provide the ﬁrst evidence indicating that a chromatin-remodeling event in T cells is impaired by aging. The Journal of Immunology, 2006, 176: 2546–2554.
Absence of RAGE protects from atherosclerosis in diabetes RAGE DEFICIENCY ATTENUATES THE DEVELOPMENT OF ATHEROSCLEROSIS IN DIABETES

This is an uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association, publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at http://diabetes.diabetesjournals. org. Diabetes Publish Ahead of Print, published online May 28, 2008
Effect of Nobiletin on Diabetic Neuropathy in Experimental Rats

function include slowing in nerve conduction velocity by axonal degeneration, paranodal demyelination and loss of myelinated fibers Long term neuropathy leads to more severe effects like severe pain, loss of sensation, foot ulceration and amputation, burns, infection, cellulites, sleep disorder, impaired daily functioning, mood disorders, gangrene, involvement of different Abstract Diabetic neuropathy (DN) is a microvascular complication of diabetes that leads to allodynia, nerve conduction slowing and progressive sensory loss. Despite the prevalence and severity of DN, currently there is no treatment available for DN. Objective of present study was to evaluate efficacy of nobiletin in the treatment of diabetic neuropathy in rats. Diabetes was induced in rats using a single dose of streptozotocin (50mg/kg i.p.). Four weeks after the induction of diabetes, treatment with nobiletin (10mg/kg and 25mg/kg) was given for further four weeks. At the end of eight weeks, the nociception latency was measured using hot plate and tail flick test. Further the nerve conduction velocity was measured and the histopathology of the sciatic nerve was studied. The results indicated that nobiletin caused improvement in nerve conduction velocity at a dose of 25mg/kg (42.58 ± 2.02** vs. control 30.00 ± 1.51) and sciatic nerve histology. The nociception latency also was improved. Thus, the study showed efficacy of nobiletin in the treatment of diabetic neuropathy in rats.
Identifying the Rhodoquinone (RQ) Biosynthetic Pathway in Search of Novel Antihelminthic Targets

Helminths infect a quarter of the world’s population. Infections caused by these parasitic nematodes, cestodes and trematodes can lead to complications such as severe malnutrition, pneumonia and liver failure. Following the ingestion of the helminth the parasites are exposed to a hypoxic environment inside the host’s digestive tract. To survive, helminths rely on an anaerobic metabolism called fumarate respiration. Fumarate respiration requires a molecule called rhodoquinone (RQ). Although RQ was discovered over 50 years ago its biosynthetic pathway is unknown. Discovering how RQ is synthesized could lead to potential targets for new antihelminthic treatments. Resistance to all classes of antihelminthic drugs has been reported and it is critical that new treatments are found. By analyzing quinone extracts from the non-parasitic nematode C. elegans using LC-MS, I have discovered the biosynthetic precursor, potential intermediates and enzymes required for RQ synthesis and its regulation.
Semimature Dendritic Cells Tolerance and CD8 T Cell Immunity by Simultaneous Induction of CD4 T Cell

Previous studies suggested that depending on their maturation state, dendritic cells (DC) could either induce T cell tolerance (immature and semimature DC) or T cell activation (mature DC). Pretreatment of C57BL/6 mice with encephalitogenic myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide-loaded semimature DC protected from MOG-induced autoimmune encephalomyelitis. This protection was mediated by IL-10-producing CD4 T cells speciﬁc for the self Ag. Here we show that semimature DC loaded with the MHC class II-restricted nonself peptide Ag (OVA) induce an identical regulatory T cell cytokine pattern. However, semimature DC loaded simultaneously with MHC class II- and MHC class I-restricted peptides, could efﬁciently initiate CD8 T cell responses leading to autoimmune diabetes in a TCR-transgenic adoptive transfer model. Double-peptide-loaded semimature DC also induced simultaneously in the same animal partially activated CD8 T cells with cytolytic function as well as protection from MOG-induced autoimmune encephalomyelitis. Our study suggests that the decision between tolerance and immunity not only depends on the DC, but also on the type and activation requirements of the responding T cell. The Journal of Immunology, 2005, 174: 3941–3947.
The Use of Emollients for Atopic Eczema

Atopic Eczema (AE) is a frequent inflammatory skin disease with chronic relapsing course. It can affect patients of all ages and have dramatic impact on their quality of life. The baseline therapy of AE is represented by environmental interventions together with topical treatment: moisturizers and emollients, corticosteroids or calcineurin inhibitors. Systemic therapy and phototherapy are reserved for severe cases. Emollients are the mainstay of first-line intervention: they hydrate and soften the skin and act as restorers or replacers of the epidermal barrier, which is often damaged or impaired in AE. Over and above the varying ingredients, formulations, strategy of action, costs and innovation, the three key-points of both the older and the latest emollients are: hydration against dryness, protection from pathogen bacterial colonization, relief from pruritus and from other symptoms. The purpose of our review was to describe the classes of emollients (firstgeneration, second-generation and third-generation emollients, together with most innovative products) and their composition (oils, ointments, creams, richin-water substances), and also to illustrate the main trials that established their efficacy and safety in adults and children. The use of emollients in AE is currently recommended with a Grade of Recommendation A and Level of Evidence I, and they can be administrated for primary prevention, as well as for acute treatment and for secondary prevention and maintenance. In conclusion, emollients are an optimal source for baseline therapy against AE, as they are appropriate and suitable for long-term schedules and for all ages. Moreover their use can lead to the control of the disease or reduce the need of topical steroids and of systemic drugs. Emollients must be used daily and consistently and they are especially appropriate for mild-moderate chronic AE.
Predictors and moderators of outcomes in mindfulness-based cognitive therapy intervention for early breast cancer patients

Objectives. To deliver mindfulness-based cognitive therapy (MBCT) efficiently, the present study aimed (1) to identify predictors and moderators of patients who benefit from MBCT for psychological distress and (2) to explore the initial treatment reaction to identify the optimal number of sessions that produce a significant clinical effect. Methods. This is the secondary analysis of a randomized controlled trial of MBCT for breast cancer patients ( N = 74). We classified the participants into remitters vs. non-remitters, and responder vs. non-responders, according to the total score of the Hospital Anxiety and Depression Scale at the end of the intervention. We conducted multivariate analyses to explore for predictors of response and remission. We adopted generalized estimating equations to explore the optimal number of sessions. Results. Sociodemographic and clinical backgrounds did not have significant influence on the treatment outcomes of the MBCT. Better program adherence, which was represented as the participants ’ better attendance to the MBCT program, was a significant predictor of both remission and response [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.25 – 2.89, p = 0.003, and OR = 1.72, 95% CI 1.12 – 2.65, p = 0.013, respectively]. It was not until seventh session that the remission rate exceeded 50% and the response rate showed significance. Significance of results. Sociodemographic and clinical characteristics the treatment outcomes, homework minutes and class attendance had significant effects treatment outcomes. This implies that MBCT is recommended to any cancer patient, if he/she is motivated to the program, regardless of their sociodemographic and clinical characteristics. Patients are encouraged to attend a standard MBCT program (eight sessions) and do the assigned homework as intensely as possible. Further studies with larger sample and objective measurements are desired. intervention
International Journal for Quality research

The education of the employees in each instance of company comes with the purpose to gain competences and experience in order to realize every business process in accordance with the requests of the products/ services, legal obligation and competitiveness criteria, as well as with the appointing of the employees requests, and all that with the intention to achieve quality where it is necessary to involve everyone in their own field. In this paper the following inputs are being given in order to get a clear picture if Macedonian companies are keen on to learning and stimulating the individual and collective learning as to improve the results in general. According to the given results in the research, it is stated that Macedonian companies do not care about the quality, insufficiently pay attention to the continuous education, make small investments in the innovations and over all, the quality system is built in a very small number of companies. In this paper the following model for a successful designing and implementing of the educational system as a subsystem of the house of quality is suggested. This methodology is integral and universal meaning it is applicable to all companies and institutions. Without a given training about TQM (Total Quality Management) philosophy and a continued education provided firstly to the managers and further on to all the employees, the TQM strategy could not be implemented as well as the benefits that come with the quality system.
Kinetics of neutralising antibodies against Omicron variant in Vietnamese healthcare workers after primary immunisation with ChAdOx1-S and booster with BNT162b2

We studied the development and persistence of neutralising antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs with different pre-existing immune statuses (group 1 (G1): n=21, and group 2 (G2): n=26 without and with prior breakthrough Delta variant infection, respectively). The study participants had completed primary immunisation with ChAdOx1-S and booster vaccination with BNT162b2. Neutralising antibodies were measured using a surrogate virus neutralisation assay. Of the 21 study participants in G1, neutralising antibodies against ancestral strain, Delta variant, BA.1 and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralising antibodies to the study viruses at week two post booster dose. Of the 26 study participants in G2, neutralising antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralising antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralising activities against ancestral strain and Delta variant, as compared to those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasise the importance of the first booster dose in producing cross-neutralising antibodies against Omicron variant. A second booster dose might be needed to maintain long-term protection against Omicron variant.
31P-MRS of healthy human brain: revealing the hidden PME signals under phosphoethanolamine and phosphocholine resonances at 7T

Purpose For decades, it has been common practice to quantify brain phosphomonoester (PME) 31P signals by a two-component model composed of phosphoethanoamine (PE) and phosphcholine (PC). This study presented the evidence of hidden PME (h-PME) signals and their selective detections toward accurate quantification of PE and PC. Methods Gaussian lineshape analysis was modeled to reveal h-PME. Inversion-recovery (IR) sequence was employed to null the PE and PC resonances for selective detection of h-PME. The fully-relaxed 31P spectra after h-PME correction were used to quantify PE, PC and other brain metabolites in a group of 16 healthy subjects. Results Spectral lineshape analysis and IR modulation revealed previously overlooked h-PME signals underlying sharp PE and PC resonances. The h-PME signals appeared as a broad bump (LW1/2: 105 +- 25 Hz, N = 16), leading to poor spectral resolution between PE and PC. Fast relaxing h-PME signals, tentatively assigned to blood 2,3-DPG, were selectively detectable using IR sequence at an optimal inversion delay of 5.8 s. In fully relaxed 31P spectra, h-PME measured 44 +- 9 % of the total PME signal, equivalent to 1.36 +- 0.39 mM in single phosphoryl unit, compared to 1.41 +- 0.23 mM for PE and 0.31 +- 0.10 mM for PC. Conclusion Hidden PME signals are a significant constitute of PME signals in human brain 31P spectra, and need to be taken into account for quantifying PE and PC as biomarkers of altered phospholipid metabolism in brain pathologies.
Overall and sex-specific effect of berberine for dyslipidemia: systematic review and meta-analysis of placebo-controlled trials

Background: Berberine is a nutraceutical that may improve lipid profiles. Berberine may also affect sex hormones and exert sex-specific effects, which has been overlooked. Objectives: To comprehensively review the efficacy and safety of lipid-lowering effect of berberine with consideration of potential sex disparity. Methods: Eligible studies were randomized controlled trials in adults that compared berberine versus placebo and measured blood lipids or lipoproteins. Studies were identified from Medline, Embase, Wanfang, CNKI, two clinical trial registries and previous systematic reviews. Mean differences (MD) were estimated using inverse variance weighting with random effects models. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Results: 16 studies were included with treatment of 4 to 24 weeks. Berberine reduced low-density lipoprotein (LDL) cholesterol (-0.45 mmol/L, 95% CI -0.60 to -0.31, 12 studies, n=1,224), total cholesterol (-0.47 mmol/L, 95% CI -0.61 to -0.33, 15 studies, n=1,397), triglycerides (-0.32 mmol/L, 95% CI -0.44 to -0.19, 16 studies, n=1,421) and apolipoprotein B (-0.25 mg/dL, 95% CI -0.40 to -0.11, 2 studies, n=127). Berberine increased high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.12, 13 studies, n=1,248). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (-0.07 mmol/L, 95% CI -0.16 to 0.02). Gastrointestinal adverse events were the most frequently reported adverse events. Conclusions: Berberine decreased LDL cholesterol, triglycerides, and apolipoprotein B, with a potential sex-specific effect on HDL cholesterol. Large-scale trials considering sex disparity are required.
Host microRNAs are differentially expressed in EBV+ Post-transplant Lymphoproliferative Disorder solid-organ transplant recipients

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. Previously, we demonstrated that EBV infection markedly reshapes the microRNA (miR) landscape in EBV+ B cell lines leading to increased IL-10 production. To establish the miRNAome of PTLD tumors we analyzed formalin-fixed, paraffin-embedded shavings of tumor tissues obtained from EBV+ PTLD SOT recipients by microarray analysis and quantitative PCR. The miRNAome of EBV+ PTLD tumors were distinctly different from EBV- PTLD tumors with reduced expression of miRs-17, 19 and 106a, and 194 among EBV+ PTLD tumors. miRs-17, 19, 106a, 155, and 194 were quantitated in the plasma and extracellular vesicles (EVs) from EBV+ PTLD+ SOT recipients and matched transplant controls. The plasma and EV levels of miRs-17, 19, 106a and 194 trended lower in the EBV+ PTLD+ group compared to matched controls, with miR-17 (plasma), miR-19 (EVs) and 106a (plasma and EVs) being significantly reduced. Importantly, the cell free miRs were contained primarily within the EVs. Further studies on the diagnostic, mechanistic, and therapeutic potential of these miRs in PTLD are warranted.