Translational research : the journal of laboratory and clinical medicine
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The prevalence of peptic ulcer diseases has decreased over the past decades. The contribution of Helicobacter pylori to these changes has not been clearly delineated. Two cohorts of patients receiving esophagogastroduodenoscopy examination together with urease test were enrolled, 1 from year 2001 (n = 1030), the other from year 2019 (n = 600). ⋯ Independent decreases of H. pylori infection, gastric ulcer and duodenal ulcer over decades were found. In H. pylori positive patients, duodenal ulcer prevalence decreased overtime while gastric ulcer prevalence remained unchanged. Gastric ulcer/cancer had a higher prevalence of MboI-defined genotype 3 UreC gene.
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Observational Study
Serum levels of the soluble urokinase plasminogen activator receptor (suPAR) correlates with disease activity in early rheumatoid arthritis and reflects joint damage over time.
Soluble urokinase plasminogen activator receptor (suPAR) is intensively studied as a biomarker of inflammation and disease outcome in various diseases. In rheumatoid arthritis (RA), suPAR have shown an association with inflammation and swollen joints, but data on suPAR in relation to early disease course and disease progression are lacking. This study investigates the potential of suPAR to predict or reflect disease outcome in early RA. ⋯ In conclusion, suPAR levels associate with disease activity in early untreated RA and reflects joint damage at later stages. Increased suPAR in established RA could indicate patients in need of frequent monitoring of joint status, irrespective of disease activity. In the view of suPAR as a rapidly emerging biomarker, it is important to be aware of its ability to reflect both inflammation and subsequent damage.
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Plasma leakage is a hallmark process in dengue viral (DENV) infection that occurs due to the loss of vascular integrity in endothelial cells. Endoglin (ENG) and Syndecan-1 (SDC-1) are released by activated endothelial cells; however, the complete dynamics of its expression at the gene and protein levels during the course of DENV infection remains unknown. In the present study, we quantified the mRNA and soluble protein levels of ENG and SDC-1 in dengue cases during febrile, defervescence, and convalescence stages in Dengue without Warning Sign (DWOW-15), Dengue with Warning Sign (DWW-22), and Severe Dengue cases (SD-10) compared to nondengue Other Febrile Illness (OFI-10) and healthy control (HC-8). ⋯ However, at the time of admission (febrile), no such significant changes were observed within dengue, OFI, and healthy controls. SVM analysis revealed that the serum levels of ENG and SDC-1 along with other clinical symptoms could predict the disease severity with 100% accuracy. Based on the results we have proposed a mechanism on how ENG and SDC-1 could be involved in vascular dysfunction rather than just being a biomarker.
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The symbiotic relationships shared between humans and their gastrointestinal parasites present opportunities to discover novel therapies for inflammatory diseases. A prime example of this phenomenon is the interaction of humans and roundworms such as the hookworm, Necator americanus. Epidemiological observations, animal studies and clinical trials using experimental human hookworm infection show that hookworms can suppress inflammation in a safe and well-tolerated way, and that the key to their immunomodulatory properties lies within their secreted proteome. ⋯ Next generation sequencing of colon tissue in the T-cell transfer model of colitis revealed that Na-AIP-1 induced a transcriptomic profile associated with the downregulation of metabolic and signaling pathways involved in type-1 inflammation, notably TNF. Finally, co-culture of Na-AIP-1 with a human monocyte-derived M1 macrophage cell line resulted in significantly reduced secretion of TNF. Na-AIP-1 is now a candidate for clinical development as a novel therapeutic for the treatment of human inflammatory bowel diseases.
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This study was aimed at generating and investigating the efficacy of a novel monoclonal bispecific antibody (BsAb) for the combined inhibition of tumor necrosis factor-α (TNF-α) and CXCL10 as a treatment option for rheumatoid arthritis (RA). A novel BsAb targeting TNF-α and CXCL10 was generated by conjugating a single-chain variable fragment (scFv) of the anti-CXCL10 monoclonal antibody to the Fc region of adalimumab (ADA). The effects of the BsAb on the inflammatory response in the in vitro and in vivo development of arthritis and joint destruction were evaluated in human TNF transgenic (hTNF-Tg) mice, and K/BxN serum transfer arthritis models. ⋯ In the K/BxN serum transfer model, BsAb effectively attenuated ankle swelling, synovial inflammation, cartilage damage, and bone destruction, reducing the activation of osteoclasts. The additional neutralization of TNF-α and CXCL10 from treatment with the novel BsAb was more effective than TNF-α inhibition alone in the in vitro and in vivo models of RA. Thus, the BsAb, targeting both TNF-α and CXCL10, may provide a new therapeutic opportunity for RA patients who fail to respond to the blockade of a single cytokine.