Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may ...contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant‐expressed miRNAs using real‐time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant‐expressed miRNAs was detected using real‐time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR‐145, miR‐224, miR‐513‐5p, miR‐150, miR‐516a‐5p, miR‐483‐5p and miR‐629, were found to be potentially abnormally expressed in SLE T cells. After validation, under‐expressed miR‐145 and over‐expressed miR‐224 were noted. We further found that STAT1 mRNA targeted by miR‐145 was over‐expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR‐224 was under‐expressed in SLE T cells. Transfection of Jurkat cells with miR‐145 suppressed STAT1 and miR‐224 transfection suppressed API5 protein expression. Over‐expression of miR‐224 facilitates activation‐induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR‐145 and miR‐224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation‐induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription‐1 (STAT)‐1 expression in patients with SLE.
Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of ...hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease.
In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (P<0.05) and by decreasing the triglyceride (TG) and total cholesterol (TC) contents of the liver (P<0.05). Oral kefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P<0.05) but not the expression of peroxisome proliferator-activated receptor α (PPARα) or hepatic carnitine palmitoyltransferase-1α (CPT1α) in the livers of ob/ob mice.
On the basis of these results, we conclude that kefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.
We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
Abstract Objectives Liver regeneration and donor safety in right-lobe (RL) and left-lobe (LL) grafts are essential for donors in living donor liver transplantation (LDLT). Our aim was to compare the ...liver regeneration rate and postoperative outcome between different donor graft types in LDLT. Materials and Methods A total of 95 donors were divided into 2 groups: RL (n = 42) and LL (n = 53). The remnant liver of LL donors were subdivided into 3 subgroups according to the different hepatic venous drainage pattern that dominates from right hepatic vein (dominant RHV; n = 34), middle hepatic vein (dominant MHV; n = 10), and include MHV for left lateral segment (LLS) graft (n = 9). The demographic data, postoperative laboratory data, complications, remnant liver volume (RLV), and remnant liver regeneration rate (RLRR) 6 months after surgery were compared. Results The postoperative total bilirubin (TB), prothrombin time (PT), and intensive care unit (ICU) stays of the LL group were lower than the RL group ( P < .05). The LL group has no significant better regeneration rate 6 months after surgery than the RL group. However, dominant RHV and LLS groups have significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively, P < .05), but no significance in the dominant MHV group. Conclusion In conclusion, different hepatic venous drainage patterns of remnant liver grafts may affect the regeneration rate in LL LDLT, especially with dominant RHV donors, may have more comparable outcomes with that of RL, and should be a favorable option during donor selection.
We report a study of the cyclotron resonance (CR) transitions to and from the unusual n=0 Landau level (LL) in monolayer graphene. Unexpectedly, we find the CR transition energy exhibits large (up to ...10%) and nonmonotonic shifts as a function of the LL filling factor, with the energy being largest at half filling of the n=0 level. The magnitude of these shifts, and their magnetic field dependence, suggests that an interaction-enhanced energy gap opens in the n=0 level at high magnetic fields. Such interaction effects normally have a limited impact on the CR due to Kohn's theorem W. Kohn, Phys. Rev. 123, 1242 (1961), which does not apply in graphene as a consequence of the underlying linear band structure.
We present the first measurements of cyclotron resonance of electrons and holes in bilayer graphene. In magnetic fields up to B=18 T, we observe four distinct intraband transitions in both the ...conduction and valence bands. The transition energies are roughly linear in B between the lowest Landau levels, whereas they follow square rootB for the higher transitions. This highly unusual behavior represents a change from a parabolic to a linear energy dispersion. The density of states derived from our data generally agrees with the existing lowest order tight binding calculation for bilayer graphene. However, in comparing data to theory, a single set of fitting parameters fails to describe the experimental results.
Abstract Objective Optimal hepatic venous tributary flow is correlated with liver function and regeneration. In left-lobe graft living donor liver transplantation, the stump of segment 5 and 8 ...hepatic veins (S5V and S8V) are ligated without performing hepatic tributary reconstruction. The aim of this article was to evaluate the different dominate hepatic vein patterns that affect left-lobe living donor safety. Materials and Methods A total of 44 donors who underwent left-lobe hepatectomy were divided into 2 groups, middle hepatic vein (MHV) dominance (group 1) and right hepatic vein (RHV) dominance (group 2), according to the dominant venous territory drainage from S5V and S8V or RHV. The clinical pathological data, postoperative laboratory data, complication, remnant liver volume and remnant liver regeneration rate at 6 months after surgery were compared. Results No difference was found in blood loss, postoperative liver function such as alanine transaminase value, complications, and hospital stays between groups. Group 1 had slightly higher total bilirubin level than group 2 (1.99 vs 1.79; P = .49). Group 2 had significantly better remnant liver regeneration rate than group 1 (89.2% vs 82.5%; P = .026). Conclusion It is important to recognize the dominant MHV group. Ligation large S5V and S8V in dominant MHV donors led to lower remnant liver regeneration in our series. This might be critical in extremely small RHV territory and potential large remnant liver congestion donors. Adjusting surgical planning, such as hepatic vein reconstruction, in this kind of donor might be appropriate for donor safety.
Background and purpose
Anosognosia and neglect may coexist in stroke patients. Neglect patients often report poor quality of life (QOL), whereas patients suffering from other cognition disorders with ...poor insight report better QOL. This study investigates the relationship between anosognosia, neglect and QOL amongst stroke survivors.
Methods
Stroke survivors who met the criteria were used as a sampling pool. Sixty stroke patients were observed in this study, amongst whom 20 patients with anosognosia and neglect (A+N+), 20 patients with neglect but not anosognosia (A−N+) and 20 patients with neither anosognosia nor neglect (A−N−) were selected from the sampling pool based on demographic characteristics matched with the A+N+ group. A questionnaire (SS‐QOL) was used to collect the QOL perceived by the stroke survivors.
Results
The perceived QOL of the A+N+ group was significantly better than those of the other groups, including the subscales of self‐care, mobility, work/productivity, upper extremity, mood, family role and social role. However, the A+N+ group had poor balance level and more fall incidents were reported.
Conclusion
The A+N+ group perceived better QOL but had more falls and poorer balance than the other groups. Health providers should work with caregivers aggressively in preventing accidents.
We have addressed the question of how different rodent species cope with the life‐threatening homeostatic challenge of dehydration at the level of transcriptome modulation in the supraoptic nucleus ...(SON), a specialised hypothalamic neurosecretory apparatus responsible for the production of the antidiuretic peptide hormone arginine vasopressin (AVP). AVP maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of AVP from SON axon terminals located in the posterior pituitary, and this is accompanied by a plethora of changes in the morphology, electrophysiological properties, biosynthetic and secretory activity of this structure. Microarray analysis was used to generate a definitive catalogue of the genes expressed in the mouse SON, and to describe how the gene expression profile changes in response to dehydration. Comparison of the genes differentially expressed in the mouse SON as a consequence of dehydration with those of the rat has revealed many similarities, pointing to common processes underlying the function‐related plasticity in this nucleus. In addition, we have identified many genes that are differentially expressed in a species‐specific manner. However, in many cases, we have found that the hyperosmotic cue can induce species‐specific alterations in the expression of different genes in the same pathway. The same functional end can be served by different means, via differential modulation, in different species, of different molecules in the same pathway. We suggest that pathways, rather than specific genes, should be the focus of integrative physiological studies based on transcriptome data.
Aims/hypothesis Numerous new genes have recently been identified in genome-wide association studies for type 2 diabetes. Most are highly expressed in beta cells and presumably play important roles in ...their function. However, these genes account for only a small proportion of total risk and there are likely to be additional candidate genes not detected by current methodology. We therefore investigated islets from the polygenic New Zealand mouse (NZL) model of diet-induced beta cell dysfunction to identify novel genes and pathways that may play a role in the pathogenesis of diabetes. Methods NZL mice were fed a diabetogenic high-fat diet (HF) or a diabetes-protective carbohydrate-free HF diet (CHF). Pancreatic islets were isolated by laser capture microdissection (LCM) and subjected to genome-wide transcriptome analyses. Results In the prediabetic state, 2,109 islet transcripts were differentially regulated (>1.5-fold) between HF and CHF diets. Of the genes identified, 39 (e.g. Cacna1d, Chd2, Clip2, Igf2bp2, Dach1, Tspan8) correlated with data from the Diabetes Genetics Initiative and Wellcome Trust Case Control Consortium genome-wide scans for type 2 diabetes, thus validating our approach. HF diet induced early changes in gene expression associated with increased cell-cycle progression, proliferation and differentiation of islet cells, and oxidative stress (e.g. Cdkn1b, Tmem27, Pax6, Cat, Prdx4 and Txnip). In addition, pathway analysis identified oxidative phosphorylation as the predominant gene-set that was significantly upregulated in response to the diabetogenic HF diet. Conclusions/interpretation We demonstrated that LCM of pancreatic islet cells in combination with transcriptional profiling can be successfully used to identify novel candidate genes for diabetes. Our data strongly implicate glucose-induced oxidative stress in disease progression.
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