As obesity rates continue to rise, the prevalence of metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), a new term for Nonalcoholic Fatty Liver Disease (NAFLD), also increases. In an aging population, it is crucial to understand the interplay between metabolic disorders, such as MetALD, and bone health. This understanding becomes particularly significant in the context of implant osseointegration.
View Article and Find Full Text PDFBlood vessel growth and osteogenesis in the skeletal system are coupled; however, fundamental aspects of vascular function in osteoblast-to-osteocyte transition remain unclear. Our study demonstrates that vascular smooth muscle cells (VSMCs), but not endothelial cells, are sufficient to drive bone marrow mesenchymal stromal cell-derived osteoblast-to-osteocyte transition via β-catenin signaling and exosome-mediated communication. We found that VSMC-derived exosomes are loaded with transcripts encoding proteins associated with the osteocyte phenotype and members of the WNT/β-catenin signaling pathway.
View Article and Find Full Text PDFMany challenges are faced in pancreatic cancer treatment due to late diagnosis and poor prognosis because of high recurrence and metastasis. Extracellular vesicles (EVs) and matrix metalloproteinases (MMPs), besides acting in intercellular communication, are key players in the cancer cell plasticity responsible for initiating metastasis. Therefore, these entities provide valuable targets for the development of better treatments.
View Article and Find Full Text PDFPurpose: Helicobacter pylori (H. pylori) is a significant risk factor for development of gastric cancer (GC), one of the deadliest malignancies in the world. However, the mechanism by which H.
View Article and Find Full Text PDFBackground: Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non-invasive stool tests can be used to verify successful H.
View Article and Find Full Text PDF: Autoimmune gastritis (AIG), characterized with the presence of anti-parietal-cell antibodies (APCA), is a risk factor for gastric cancer. However, AIG may go underdiagnosed, especially in the case of infection and the presence of gastric precancerous lesions (GPL), due to the ambiguous pathology and delayed symptom onset. : Investigate the prevalence and characteristics of AIG in GPL patients.
View Article and Find Full Text PDFMolecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available.
View Article and Find Full Text PDFBackground: Previous evidence indicated that -induced inflammation is the first step towards gastric carcinogenesis. However, investigations of the immunological factors driving this process have shown inconsistencies. We aimed to present a thorough summary of all researched cytokines in relation to infection and GC and relate these to global GC risk.
View Article and Find Full Text PDFSecretin-stimulated pancreatic juice (PJ), collected from the duodenum, presents a valuable biomarker source for the (earlier) detection of pancreatic cancer (PC). Here, we evaluate the feasibility and performance of shallow sequencing to detect copy number variations (CNVs) in cell-free DNA (cfDNA) from PJ for PC detection. First, we confirmed the feasibility of shallow sequencing in PJ (n = 4), matched plasma (n = 3) and tissue samples (n = 4, microarray).
View Article and Find Full Text PDFBackground And Aims: Indoleamine 2,3 dioxygenase-1 (IDO1), a key enzyme in tryptophan metabolism, is strongly up-regulated both in human inflammatory bowel disease (IBD) and animal models of colitis, however its role in the pathogenesis is still controversial. In this study, we investigated IDO1 expression and activity in a mouse model of DSS-induced chronic colitis as well as in colon biopsies and sera from IBD patients.
Methods: Chronic colitis was induced in mice through the oral administration of dextran sodium sulfate (DSS), and IDO1 activity was induced by i.
Background: New cell-based therapies are under investigation to improve perianal fistulizing Crohn's disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn's disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown.
View Article and Find Full Text PDFBackground: An unmet need remains for improved management in perianal fistulising Crohn's disease (pCD). Recently, local administration of adipose-derived cells has shown promising results.
Aims: To assess the safety and feasibility of injection of stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in patients with pCD.
Intelectin-1 (ITLN1) is a lectin secreted by intestinal epithelial cells (IECs) and upregulated in human ulcerative colitis (UC). We investigated how ITLN1 production is regulated in IECs and the biological effects of ITLN1 at the host-microbiota interface using mouse models. Our data show that ITLN1 upregulation in IECs from UC patients is a consequence of activating the unfolded protein response.
View Article and Find Full Text PDFBackground: Ustekinumab (UST), which targets p40/interleukin (IL)-23 and IL-12, is an effective treatment for Crohn's disease (CD). Therapeutic drug monitoring may optimize UST posology. The aim of this study was to investigate UST and IL-23 serum and tissue concentrations in relation to mucosal inflammation and treatment response at an early time point.
View Article and Find Full Text PDFIntroduction: Gastric intestinal metaplasia (GIM) is a premalignant lesion, highly associated with Helicobacter pylori infection. Previous studies have shown that H. pylori is able to induce the expression of programmed death ligand 1 (PD-L1), an inhibitory immune modulator, in gastric cells.
View Article and Find Full Text PDFBackground And Aims: Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival.
View Article and Find Full Text PDFBackground: Cholangiocarcinoma is a rare but lethal cancer of the biliary tract. Its first-line treatment is currently restricted to chemotherapy, which provides limited clinical benefit. Kinase inhibitors targeting oncogenic intracellular signaling have changed the treatment paradigm of cancer over the last decades.
View Article and Find Full Text PDFIntroduction: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in an advanced stage, with minimal likelihood of long-term survival. Only a small subset of patients are diagnosed with early (T1) disease. Early detection is challenging due to the late onset of symptoms and limited visibility of sub-centimeter cancers on imaging.
View Article and Find Full Text PDF