80 research outputs found
Recommended from our members
Neuropilinā1 as a new potential SARSāCoVā2 infection mediator implicated in the neurologic features and central nervous system involvement of COVIDā19
Availability of data and materials:
All data generated or analysed during this study are included in this published article.Copyright Ā© 2020 Davies et al. Infection by the severe acute respiratory syndrome (SARS) coronavirusā2 (SARSāCoVā2) is the cause of the new viral infectious disease (coronavirus disease 2019; COVIDā19). Emerging evidence indicates that COVIDā19 may be associated with a wide spectrum of neurological symptoms and complications with central nervous system (CNS) involvement. It is now wellāestablished that entry of SARSāCoVā2 into host cells is facilitated by its spike proteins mainly through binding to the angiotensināconverting enzyme 2 (ACEā2). Preclinical studies have suggested that neuropilinā1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVIDā19 by enhancing the entry of SARSāCoVā2 into the brain through the olfactory epithelium. In the present study, we expand on these findings and demonstrate that the NRP1 is also expressed in the CNS, including olfactoryārelated regions such as the olfactory tubercles and paraolfactory gyri. This furthers supports the potential role of NRP1 as an additional SARSāCoVā2 infection mediator implicated in the neurologic manifestations of COVIDā19. Accordingly, the neurotropism of SARSāCoVā2 via NRP1āexpressing cells in the CNS merits further investigation.No funding was received
Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose
This is the final version of the article. Available from the publisher via the DOI in this record.OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.This work was supported by Diabetes UK, Swedish Research
Council (11285), University Hospital of Linkoping
Research Funds; Diabetes Research Centre of Linkoping
University; and the Gamla Tjaenarinnor Foundation.
No potential conflicts of interest relevant to this article
were reported.
Parts of this study were presented in abstract form at
the 69th Scientific Sessions of the American Diabetes
Association, New Orleans, Louisiana, 5ā9 June 2009
A pancancer overview of FBN1, asprosin and its cognate receptor OR4M1 with detailed expression profiling in ovarian cancer
Copyright : Ā© Kerslake et al. Ovarian cancer affects >295,000 women worldwide and is the most lethal of gynaecological malignancies. Often diagnosed at a late stage, current research efforts seek to further the molecular understanding of its aetiopathogenesis and the development of novel biomarkers. The present study investigated the expression levels of the glucogenic hormone asprosin [encoded by fibrillinā1 (FBN1)], and its cognate receptor, olfactory receptor 4M1 (OR4M1), in ovarian cancer. A blend of in silico open access The Cancer Genome Atlas data, as well as in vitro reverse transcriptionāquantitative PCR (RTāqPCR), immunohistochemistry and immunofluorescence data were used. RTāqPCR revealed expression levels of OR4M1 and FBN1 in clinical samples and in ovarian cancer cell lines (SKOVā3, PEO1, PEO4 and MDAHā2774), as well as the normal human ovarian surface epithelial cell line (HOSEpiC) . Immunohistochemical staining of a tissue microarray was used to identify the expression levels of OR4M1 and asprosin in ovarian cancer samples of varying histological subtype and grade, including clear cell carcinoma, serous ovarian cancer and mucinous adenocarcinoma. Immunofluorescence analysis revealed asprosin expression in SKOVā3 and HOSEpiC cells. These results demonstrated the expression of both asprosin and OR4M1 in normal and malignant human ovarian tissues. This research invokes further investigation to advance the understanding of the role of asprosin and OR4M1 within the ovarian tumour microenvironment.Cancer Treatment & Research Trust and University Hospitals Coventry and Warwickshire NHS Trus
Recommended from our members
NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue
Data Availability Statement: Data are available via the corresponding authors upon reasonable request that does not raise any ethical, privacy, or security concerns.Copyright: Ā© 2022 by the authors. Background: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. Methods: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 Āµg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. Results: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (TnfĪ±, Il-6, Il-1Ī², Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (TnfĪ±, Il-6, Il-1Ī², Mcp1) and hmgb1. Conclusion: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT.This research received no external funding
Asprosin Exerts Pro-Inflammatory Effects in THP-1 Macrophages Mediated via the Toll-like Receptor 4 (TLR4) Pathway
Data Availability Statement:
Data are contained within the paper and its Supplementary Material: the following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ijms24010227/s1.Copyright Ā© 2022 by the authors. Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 Ī¼M caffeic acid phenethyl ester (CAPE; an inhibitor of NFĪŗB activation) or 1 ĀµM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor Ī± (TNFĪ±), interleukin-1Ī² (IL-1Ī²), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway.University Hospitals Coventry and Warwickshire (UHCW) NHS Trust; Aston University (grant: number: Aston University 50th Anniversary Prize PhD Studentships Scheme)
Protein expression of transmembrane protease serine 4 in the gastrointestinal tract and in healthy, cancer, and SARSāCoVā2 infected lungs
Availability of data and materials:
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Copyright: Ā© Kerslake et al. In addition to the angiotensināconverting enzyme 2 (ACE2), a number of host cell entry mediators have been identified for severe acute respiratory syndrome coronavirusā2 (SARSāCoVā2), including transmembrane protease serine 4 (TMPRSS4). The authors have recently demonstrated the upregulation of TMPRSS4 in 11 different cancers, as well as its specific expression within the central nervous system using in silico tools. The present study aimed to expand the initial observations and, using immunohistochemistry, TMPRSS4 protein expression in the gastrointestinal (GI) tract and lungs was further mapped. Immunohistochemistry was performed on tissue arrays and lung tissues of patients with nonāsmall cell lung cancer with concurrent coronavirus disease 2019 (COVIDā19) infection using TMPRSS4 antibody. The results revealed that TMPRSS4 was abundantly expressed in the oesophagus, stomach, small intestine, jejunum, ileum, colon, liver and pancreas. Moreover, the extensive TMPRSS4 protein expression in the lungs of a deceased patient with COVIDā19 with chronic obstructive pulmonary disease and bronchial carcinoma, as well in the adjacent normal tissue, was demonstrated for the first time, at least to the best of our knowledge. On the whole, the immunohistochemistry data of the present study suggest that TMPRSS4 may be implicated in the broader (pulmonary and extraāpulmonary) COVIDā19 symptomatology; thus, it may be responsible for the tropism of this coronavirus both in the GI tract and lungs.Cancer Treatment and Research Trust; University Hospitals Coventry and Warwickshire NHS Trust (grant no. 12899)
The role of mindfulness training in sustaining weight reduction: retrospective cohort analysis
Background Psychological stress has an established bi-directional relationship with obesity. Mindfulness techniques reduce stress and improve eating behaviours, but their long-term impact remains untested. CALMPOD (Compassionate Approach to Living Mindfully for Prevention of Disease) is a psychoeducational mindfulness-based course evidenced to improve eating patterns across a 6-month period, possibly by reducing stress. However, no long-term evaluation of impact exists. Aims This study retrospectively evaluates 2-year outcomes of CALMPOD on patient engagement, weight and metabolic markers. Method All adults with a body mass index >35 kg/m2 attending an UK obesity service during 2016ā2020 were offered CALMPOD. Those who refused CALMPOD were offered standard lifestyle advice. Routine clinic data over 2 years, including age, gender, 6-monthly appointment attendance, weight, haemoglobin A1C and total cholesterol, were pooled and analysed to evaluate CALMPOD. Results Of 289 patients, 163 participated in the CALMPOD course and 126 did not. No baseline demographic differences existed between the participating and non-participating groups. The CALMPOD group had improved attendance across all 6-monthly appointments compared with the non-CALMPOD group (P < 0.05). Mean body weight reduction at 2 years was 5.6 kg (s.d. 11.2, P < 0.001) for the CALMPOD group compared with 3.9 kg (s.d. 10.5, P < 0.001) for the non-CALMPOD group. No differences in haemoglobin A1C and fasting serum total cholesterol were identified between the groups. Conclusions The retrospective evaluation of CALMPOD suggests potential for mindfulness and compassion-based group educational techniques to improve longer-term patient and clinical outcomes. Prospective large-scale studies are needed to evaluate the impact of stress on obesity and the true impact of CALMPOD. </jats:sec
- ā¦