Αρχειοθήκη ιστολογίου

Κυριακή 19 Δεκεμβρίου 2021

Iron Deficiency Is Associated with Maternal Hypothyroxinemia in the Third Trimester of Pregnancy

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Clinical Thyroidology, Volume 33, Issue 12, Page 526-528, December 2021.
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Obesity Is Associated with Increased Adipocyte Infiltration in the Thyroid Tissue: A New Perspective?

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Clinical Thyroidology, Volume 33, Issue 12, Page 516-519, December 2021.
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Replication of epidemiological associations of carpal tunnel syndrome in a UK population-based cohort of over 400,000 people

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J Plast Reconstr Aesthet Surg. 2021 Nov 14:S1748-6815(21)00571-4. doi: 10.1016/j.bjps.2021.11.025. Online ahead of print.

ABSTRACT

INTRODUCTION: Several phenotypic factors are associated in the literature with an increased risk of carpal tunnel syndrome (CTS). Along with female sex and older age, certain systemic diseases show an association with CTS, with varying degrees of evidence.

METHODS: This study was performed using the UK Biobank resource - a cohort study of over 500,000 participants who have allowed linkage of phenotypic data with their medical records. We calculated the prevalence of CTS and a sex-specific prevalence ratio and compared the body mass index (BMI) between cases and controls. We performed a series of nested case-control studies to compute odds ratios for the association between CTS and three systemic diseases.

RESULTS: There were 12,312 CTS cases within the curated UK Biobank dataset of 401,656 (3.1% prevalence), and the female:male ratio was 1.95:1. CTS cases had, on average, a BMI > 2.0 kg/m2 greater than controls. Odds ratios for the association with CTS for three systemic diseases were 2.31 (95% CI 2.17-2.46) for diabetes, 2.70 (95% CI 2.44-2.99) for rheumatoid arthritis, and 1.47 (95% CI 1.38-1.57) for hypothyroidism. Adjusted for BMI, these odds ratios fell to 1.75 (95% CI 1.65-1.86), 2.43 (95% CI 2.20-2.69), and 1.35 (95% CI 1.26-1.43), respectively.

DISCUSSION: We harnessed the size and power of UK Biobank to provide robust replication of evidence for the associations between CTS and female sex, raised BMI, and three systemic diseases, which are only mediated in part by raised BMI.

PMID:34916160 | DOI:10.1016/j.bjps.2021.11.025

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Identification of potential biomarkers for diagnosis of hepatocellular carcinoma

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Exp Ther Med. 2022 Jan;23(1):51. doi: 10.3892/etm.2021.10973. Epub 2021 Nov 15.

ABSTRACT

Hepatocellular carcinoma (HCC) has a high mortality rate owing to its complexity. Identification of abnormally expressed genes in HCC tissues compared to those in normal liver tissues is a viable strategy for investigating the mechanisms of HCC tumorigenesis and progression as a means of developing novel treatments. A significant advantage of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) is that the data therein were collected from different independent researchers and may be integrated, allowing for a more robust data analysis. Accordingly, in the present study, the gene expression profiles for HCC and control samples were downloaded from the GEO and TCGA. Functional enrichment analysis was performed using a Metascape dataset, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retri eval of Interacting Genes/proteins (STRING) online database. The prognostic value of mRNA for HCC was assessed using the Kaplan-Meier Plotter, a public online tool. A gene mRNA heatmap and DNA amplification numbers were obtained from cBioPortal. A total of 2,553 upregulated genes were identified. Functional enrichment analysis revealed that these differentially expressed genes (DEGs) were mainly accumulated in metabolism of RNA and the cell cycle. Considering the complexity and heterogeneity of the molecular alterations in HCC, multiple genes for the prognostication of patients with HCC are more reliable than a single gene. Thus, the PPI network and univariate Cox regression analysis were applied to screen candidate genes (small nuclear ribonucleoprotein polypeptide B and B1, nucleoporin 37, Rac GTPase activating protein 1, kinesin family member 20A, minichromosome maintenance 10 replication initiation factor, ubiquitin conjugating enzyme E2 C and hyaluronan mediated motility recept or) that are associated with the overall survival and progression-free survival of patients with HCC. In conclusion, the present study identified a set of genes that are associated with overall survival and progression-free survival of patients with HCC, providing valuable information for the prognosis of HCC.

PMID:34917180 | PMC:PMC8630445 | DOI:10.3892/etm.2021.109 73

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HIF-1α mediates the protective effect of plasma extracellular particles induced by remote ischaemic preconditioning on oxidative stress injury in human umbilical vein endothelial cells

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Exp Ther Med. 2022 Jan;23(1):48. doi: 10.3892/etm.2021.10970. Epub 2021 Nov 15.

ABSTRACT

Remote ischaemic preconditioning (RIPC) is considered to alleviate myocardial ischaemia/reperfusion (I/R) injury. The present study explored whether blood plasma particulate matter, which is termed extracellular particles (EPs), and is released from cells during RIPC, could reduce H2O2-induced damage in human umbilical vein endothelial cells (HUVECs). Firstly, EPs were derived from volunteers who did or did not undergo RIPC. To induce RIPC in volunteers, a blood pressure cuff was alternatively inflated for 5 min and deflated for the same duration for four successive cycles. HUVECs were assigned to two groups: i) Group 1 was preincubated for 24 h with EPs from volunteers after sham-RIPC, then treated with H2O2 (1 mM; 6 h) to mimic the in vivo conditions of I/R-induced oxidative stress; and ii) group 2 was preincubated for 24 h with EPs from volunteers after RIPC, then treated with H2O2. Subsequently, EPs were derived from rats received sham-RIPC or RIPC and/or cadmium (Cd) pre-treatment. To induce RIPC in rats, a remote hind limb preconditioning stimulus was delivered using a blood pressure cuff attached at the inguinal level of the rat. The blood pressure cuff was alternatively inflated for 5 min and deflated for the same time period for four successive cycles. HUVECs were assigned to six groups: i) Group 1 was untreated; ii) group 2 received only H2O2 treatment (1 mM; 6 h); iii) group 3 was preincubated for 24 h with EPs from rats exposed to sham-RIPC, then treated with H2O2; iv) group 4 was preincubated for 24 h with EPs from rats that received an intraperitoneal injection of 1 mg/kg Cd [a pharmacological inhibitor of hypoxia-inducible factor 1-α (HIF-1α) in vivo] 180 min before sham-RIPC, then treat ed with H2O2; v) group 5 was preincubated for 24 h with EPs from rats exposed to RIPC, then treated with H2O2; and vi) group 6 was preincubated for 24 h with EPs from rats that received an intraperitoneal injection of 1 mg/kg Cd 180 min before RIPC, then treated with H2O2. Cell viability and cytotoxicity were monitored using Cell Counting Kit-8 and lactate dehydrogenase assays. Cell apoptosis and necrosis were assessed via flow cytometry and western blot analysis. A notable increase in EP concentration in the plasma of volunteers after RIPC compared with that in the plasma of volunteers after sham-RIPC was observed. RIPC-associated EPs (RIPC-EPs) from volunteers could improve cell viability and reduce cytotoxicity, cell apoptosis and necrosis in HUVECs treated with H2O2 in vitro. Furthermore, RIPC caused a significant increase in HIF-1α expression in the rat limb musculature. The apoptosi s-reducing effect of RIPC-EPs was demonstrated to be counteracted by an intraperitoneal injection of Cd before RIPC in rats. A significant decrease in the EP levels precipitated from the plasma of rats that received Cd treatment before RIPC was observed compared with rats that did not receive Cd treatment. The present study suggested that HIF-1α mediated at least partly the protective effect of plasma RIPC-EPs on oxidative stress injury in HUVECs.

PMID:34917179 | PMC:PMC8630 441 | DOI:10.3892/etm.2021.10970

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Circulating Tumor DNA Harboring the BRAFV600E Mutation May Predict Poor Outcomes of Primary Papillary Thyroid Cancer Patients

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Thyroid, Volume 31, Issue 12, Page 1822-1828, December 2021.
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Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1740622

Background Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Guanylin ligand protects the intestinal immune barrier by activating the guanylate cyclase-C signaling pathway

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Acta Histochem. 2021 Dec 14;124(1):151811. doi: 10.1016/j.acthis.2021.151811. Online ahead of print.

ABSTRACT

Inflammatory bowel disease (IBD) impacts patient quality of life significantly. The dysfunction of intestinal immune barrier is closely associated with IBD. The guanylate cyclase-C (GC-C) signaling pathway activated by the guanylin (Gn) ligand is involved in the occurrence and development of IBD. However, how it regulates the intestinal immune barrier is still unclea r. To investigate the effect of the GC-C pathway on intestinal mucosal immunity and provide experimental basis for seeking new therapeutic strategies for IBD, we focused on Caco-2 cells and intestinal intra-epithelial lymphocytes (IELs), which displayed inflammatory responses induced by lipopolysaccharide (LPS). GC-C activity was modulated by transfection with Gn overexpression or GC-C shRNA plasmid. Levels of Gn, GC-C, and CFTR; transepithelial electrical resistance (TER); paracellula r permeability; and levels of IL-2, IFN-γ, and secretory IgA (sIgA) were examined. The study found that after stimulation with LPS, Gn, GC-C, CFTR, TER, and sIgA levels were all significantly reduced, IL-2 and IFN-γ levels as well as paracellular permeability were significantly increased. These indicators changed inversely and significantly after transfection with the Gn overexpression vector. Compared to the vector controls, GC-C-silenced cells displayed significantly decreased levels of GC-C, CFTR , and TER and increased levels of IL-2, IFN-γ, and paracellular permeability stimulated by LPS. The results show that Gn ligand can protect the intestinal immune barrier by activating the GC-C signaling pathway, which may be helpful for the development of new treatments for IBD. DATA AVAILABILITY STATEMENT: The data used to support the findings of this study are available from the corresponding author upon request.

PMID:34920371 | DOI:10.1016/j.acthis.2021.151811

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Bispecific antibodies targeting CD3 in oncology and hematology

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Bull Cancer. 2021 Oct;108(10S):S181-S194. doi: 10.1016/j.bulcan.2021.06.003.

ABSTRACT

Bispecific therapies targeting CD3, so-called T-cell engagers (TCE), belong to the new spectrum of anti-tumor immunotherapies stimulating T-lymphocytes. TCE are unique constructs targeting the MHC-independent CD3 epsilon subunit (CD3e) and a tumor antigen. To date, only blinatumomab have reached market agreements in lymphoid malignancies with constructs targeting CD3exCD19. Other TCE are in advances development, with promising results targeting CD20 and BSMA in lymphoma and myeloma. These successes have relaunched the development of TCE in solid tumors, bringing mixed results so far (notably in terms of tolerance). Still, TCE pave the way to new immunotherapy in tumors considered to be refractory to inhibitors of immune checkpoints such as prostate cancer or colorectal cancer.

PMID:34920802 | DOI:10.1016/j.bulcan.2021.06.003

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CAR-T cells, from principle to clinical applications

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Bull Cancer. 2021 Oct;108(10S):S4-S17. doi: 10.1016/j.bulcan.2021.02.017.

ABSTRACT

Chimeric antigen receptors (CAR)-T cells are genetically engineered T-lymphocytes redirected with a predefined specificity to any target antigen, in a non-HLA restricted manner, therefore combining antibody-type specificity with effector T-cell function. This strategy was developed some thirty years ago, after extensive work established the key role of the immune system against cancer. The first-engineered T-cell with chimeric molecule was designed in 1993 by Israeli immunologist Zelig Eshhar. Since then, several modifications took place, including the addition of co-stimulatory domain, to further improve CAR-T cell anti-tumor potency. The first clinical application of CAR-T cell was done in Rotterdam in 2005 for metastatic renal cell carcinoma and simultaneously at the National Cancer Institute (NCI) for metastatic ovarian cancer. These pioneered studie s failed to demonstrate a therapeutic benefit, but warning emerged concerning their safety of use. The real clinical success came with anti-CD19 CAR-T cells, used since 2009 by Steven Rosenberg at the NCI in a patient with refractory follicular lymphoma and in 2011 by Carl June and David Porter from the University of Pennsylvania in patients with chronic lymphocytic leukemia and B-cell acute lymphoblastic leukemia. From that time, large centers in North America have embarked in several early phase and pivotal trials that have demonstrated unprecedent response rate in heavily pretreated chemo refractory patient with B-cell malignancies. Theses clinical success have led to the approval of three anti-CD19 CAR-T cells products for the management of B-cell malignancies in the United States and in Europe as of December 2020.

PMID:34920806 | DOI:10.1016/j.bulcan.2021.02.017

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CARTi: The French-speaking group for the harmonization of immune monitoring in patients treated with CAR-T cells

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Bull Cancer. 2021 Oct;108(10S):S141-S142. doi: 10.1016/j.bulcan.2021.06.006.

NO ABSTRACT

PMID:34920796 | DOI:10.1016/j.bulcan.2021.06.006

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