expression

BACKGROUND: Currently, it is acknowledged that vitamin E, insulin sensitizers and anti-diabetic drugs are used to manage non-alcoholic fatty liver disease (NAFLD), however, these therapeutic interventions harbour adverse side effects. Pioglitazone, an anti-diabetic drug, is currently the most effective therapy to manage NAFLD. The use of natural medicines is widely embraced due to the lack of evidence of their negative side effects. Rooibos has been previously shown to decrease inflammation and oxidative stress in experimental models of diabetes, however, this is yet to be explored in a setting of NAFLD...

Population differences in risk of disease are common, but the potential genetic basis for these differences is not well understood. A standard approach is to compare genetic risk across populations by testing for mean differences in polygenic scores, but existing studies that use this approach do not account for statistical noise in effect estimates (i.e., the GWAS betas) that arise due to the finite sample size of GWAS training data. Here, we show using Bayesian polygenic score methods that the level of uncertainty in estimates of genetic risk differences across populations is highly dependent on the GWAS training sample size, the polygenicity (number of causal variants), and genetic distance (FST) between the populations considered...

Communication about life-threatening disease and palliative care is essential but often experienced as difficult by those concerned and has mainly been studied in terms of its verbal components. Despite the fundamentality of nonverbal communication, its dimensions in care, especially in the communication by patients and their significant others, has not been as extensively examined. Drawing on a secondary qualitative content analysis of data from 23 interviews-15 with patients in specialized palliative home care in Sweden and 8 with their significant others-this study aims at understanding and characterizing how patients verbally express experiences of conveying nonverbal cues about life-threatening disease and its consequences and how their significant others express perceiving these cues...

BACKGROUND: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. PATIENTS AND METHODS: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial...

AIM OF THE STUDY: To evaluate the therapeutic effect of SYNC in diarrhea irritable bowel syndrome (IBS-D) and explore its underlying mechanism through transcriptomic sequencing (RNA-Seq). MATERIALS AND METHODS: A rat model of IBS-D was constructed to elucidate the effects of SYNC. Abdominal withdrawal reflex (AWR), fecal water content (FWC), and recording body weight were calculated to assess visceral sensitivity in rats. Histopathological changes in the colon and alterations in mast cell (MC) count were determined...

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs...

Although anti-citrullinated protein autoantibodies (ACPAs) are a hallmark serological feature of rheumatoid arthritis (RA), the mechanisms and cellular sources behind the generation of the RA citrullinome remain incompletely defined. Peptidylarginine deiminase IV (PAD4), one of the key enzymatic drivers of citrullination in the RA joint, is expressed by granulocytes and monocytes; however, the subcellular localization and contribution of monocyte-derived PAD4 to the generation of citrullinated autoantigens remain underexplored...

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear...

The tight control of proliferating keratinocytes is vital to the successful function of the skin. Differentiation of dividing cells is necessary to form a skin barrier. The same dividing cells are necessary to heal wounds and when malignant form tumors. RIPK4, a serine-threonine kinase, plays critical roles in these processes. Its loss of function was associated with pathological keratinocyte proliferation and development of squamous cell carcinoma (SCC) in humans and mice. The current study extends previous findings in the importance of RIPK4 in keratinocyte proliferation...

The aim of the paper is to provide an ex-post assessment of the impact of the COVID-19 pandemic on food insecurity in the EU-27 countries expressed by physical and economic food access. We analysed trade and price effects, together with food insecurity and malnutrition indicators. Actual levels of the indicators were compared with their pre-pandemic magnitudes and/or with counterfactual levels derived from predictive models. We also aimed to compare the objective statistics with the subjective consumers' perception of their households' food security...

Many oncology antibody-drug conjugates (ADCs) have failed to demonstrate efficacy in clinic because of dose-limiting toxicity caused by uptake into healthy tissues. We developed an approach that harnesses ADC affinity to broaden the therapeutic index (TI) using two anti-mesenchymal-epithelial transition factor (MET) monoclonal antibodies (mAbs) with high affinity (HAV) or low affinity (LAV) conjugated to monomethyl auristatin E (MMAE). The estimated TI for LAV-ADC was at least 3 times greater than the HAV-ADC...

In this work, a Python framework for characteristic feature extraction is developed and applied to gene expression data of human fibroblasts. Unlabeled feature selection objectively determines groups and minimal gene sets separating groups. ML explainability methods transform the features correlating with phenotypic differences into causal reasoning, supported by further pipeline and visualization tools, allowing user knowledge to boost causal reasoning. The purpose of the framework is to identify characteristic features that are causally related to phenotypic differences of single cells...

Cancer cachexia causes skeletal muscle atrophy, impacting the treatment and prognosis of patients with advanced cancer, but no treatment has yet been established to control cancer cachexia. We demonstrated that transcutaneous application of carbon dioxide (CO2) could improve local blood flow and reduce skeletal muscle atrophy in a fracture model. However, the effects of transcutaneous application of CO2 in cancer-bearing conditions are not yet known. In this study, we calculated fat-free body mass (FFM), defined as the skeletal muscle mass, and evaluated the expression of muscle atrophy markers and uncoupling protein markers as well as the cross-sectional area (CSA) to investigate whether transcutaneous application of CO2 to skeletal muscle could suppress skeletal muscle atrophy in cancer-bearing mice...

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. However, the HCC treatment is still challenging. Herein, we aimed to reveal the anti-tumor effect of Jolkinolide B in HCC cell lines Huh-7 and SK-Hep-1. The results showed that Jolkinolide B inhibited the migration, invasion, and epithelial-to-mesenchymal transition(EMT) of HCC cells. In addition, Jolkinolide B induced HCC cell apoptosis by upregulating Bax and downregulating BCL-2 expressions. Furthermore, we demonstrated that Jolkinolide B inactivated the β-catenin signaling and reduced Musashi-2 expression...

Domains as functional protein units and their rearrangements along the phylogeny can shed light on the functional changes of proteomes associated with the evolution of complex traits like eusociality. This complex trait is associated with sterile soldiers and workers, and long-lived, highly fecund reproductives. Unlike in Hymenotpera (ants, bees, and wasps), the evolution of eusociality within Blattodea, where termites evolved from within cockroaches, was accompanied by a reduction in proteome size, raising the question of whether functional novelty was achieved with existing rather than novel proteins...

Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodeling and fibrosis. Mast cells release preformed mediators (e.g., histamine, tryptase, chymase) and de novo synthesized mediators [e...

BACKGROUND: Exposure to obesogenic chemicals has been reported to result in enhanced adipogenesis, higher adipose tissue accumulation, and reduced ovarian hormonal synthesis and follicular function. We have reported that organotins [tributyltin (TBT) and triphenyltin (TPT)] dysregulate cholesterol trafficking in ovarian theca cells, but, whether organotins also exert lipogenic effects on ovarian cells remains unexplored. OBJECTIVE: We investigated if environmentally relevant exposures to organotins [TBT, TPT, or dibutyltin (DBT)] induce lipid dysregulation in ovarian theca cells and the role of the liver X receptor (LXR) in this effect...

High-penetrance mutations affecting mental health can involve genes ubiquitously expressed in the brain. Whether the specific patterns of dysfunctions result from ubiquitous circuit deficits or might reflect selective vulnerabilities of targetable subnetworks has remained unclear. Here, we determine how loss of ubiquitously expressed fragile X mental retardation protein (FMRP), the cause of fragile X syndrome, affects brain networks in Fmr1y/- mice. We find that in wild-type mice, area-specific knockout of FMRP in the adult mimics behavioral consequences of area-specific silencing...

Penihemeroterpenoids A-C, the first meroterpenoids with an unprecedented 6/5/6/5/5/6/5 heptacyclic ring system, together with precursors penihemeroterpenoids D-F, were co-isolated from the fungus Penicillium herquei GZU-31-6. Among them, penihemeroterpenoids C-F exhibited lipid-lowering effects comparable to those of the positive control simvastatin by the activation of the AMPK/ACC/SREBP-1c signaling pathway, downregulated the mRNA levels of lipid synthesis genes FAS and PNPLA3, and increased the level of mRNA expression of the lipid export gene MTTP...

ZCCHC17 is a master regulator of synaptic gene expression and has recently been shown to play a role in splicing of neuronal mRNA. We previously showed that ZCCHC17 protein declines in Alzheimer's disease (AD) brain tissue before there is significant gliosis and neuronal loss, that ZCCHC17 loss partially replicates observed splicing abnormalities in AD brain tissue, and that maintenance of ZCCHC17 levels is predicted to support cognitive resilience in AD. Here, we assessed the functional consequences of reduced ZCCHC17 expression in primary cortical neuronal cultures using siRNA knockdown...