-
Nature Reviews. Immunology Jun 2024Following the seminal discovery of insulin a century ago, treatment of individuals with type 1 diabetes (T1D) has been largely restricted to efforts to monitor and treat... (Review)
Review
Following the seminal discovery of insulin a century ago, treatment of individuals with type 1 diabetes (T1D) has been largely restricted to efforts to monitor and treat metabolic glucose dysregulation. The recent regulatory approval of the first immunotherapy that targets T cells as a means to delay the autoimmune destruction of pancreatic β-cells highlights the critical role of the immune system in disease pathogenesis and tends to pave the way for other immune-targeted interventions for T1D. Improving the efficacy of such interventions across the natural history of the disease will probably require a more detailed understanding of the immunobiology of T1D, as well as technologies to monitor residual β-cell mass and function. Here we provide an overview of the immune mechanisms that underpin the pathogenesis of T1D, with a particular emphasis on T cells.
Topics: Diabetes Mellitus, Type 1; Humans; Insulin-Secreting Cells; Animals; T-Lymphocytes; Immunotherapy; Autoimmunity
PubMed: 38308004
DOI: 10.1038/s41577-023-00985-4 -
Frontiers in Endocrinology 2023Coronavirus disease 2019 (COVID-19) caused a major pandemic affecting human health and economy around the world since the beginning of 2020. The virus responsible for... (Review)
Review
Coronavirus disease 2019 (COVID-19) caused a major pandemic affecting human health and economy around the world since the beginning of 2020. The virus responsible for the disease is "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). It invades the target cells by binding to angiotensin-converting enzyme 2 (ACE2). ACE2 is expressed in several organs including endocrine glands. Multiple endocrine and metabolic systems including the endocrine pancreas have been impacted by COVID-19 infection/pandemic. COVID-19 pandemic can promote obesity through alterations in lifestyle (e.g., unhealthy diet and reduced physical activity due to confinement and isolation) leading to type 2 diabetes and/or can directly impair the function of the endocrine pancreas particularly through a cytokine storm, promoting or aggravating type 1 or type 2 diabetes. The increased ACE2 receptors of high adiposity commonly associated with type 2 diabetes and the chronic hyperglycemia of diabetes with its negative impact on the immune system can increase the risk of COVID-19 infection and its morbidity/mortality. In conclusion, there are bidirectional interactions between COVID-19 pandemic and diabetes (e.g., COVID-19 infection can impact diabetes and diabetes can impact COVID-19 infection). The services offered by healthcare systems for the management of diabetes have been adapted accordingly.
Topics: Humans; COVID-19; SARS-CoV-2; Renin-Angiotensin System; Angiotensin-Converting Enzyme 2; Peptidyl-Dipeptidase A; Diabetes Mellitus, Type 2; Pandemics
PubMed: 38292772
DOI: 10.3389/fendo.2023.1306290 -
Endoscopy International Open Jan 2024This retrospective study aimed to investigate risk factors for early adverse events (AEs) associated with endoscopic ultrasonography-guided hepaticogastrostomy...
This retrospective study aimed to investigate risk factors for early adverse events (AEs) associated with endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) using self-expandable metal stents (SEMS). The clinical success rate, technical success rate, and early AEs were assessed at two hospitals from 2010 to 2022. The analysis focused on risk factors associated with cholangitis, peritonitis, and SEMS migration. Technical success was achieved in all cases (94/94), and clinical success was 96.8% (91/94). Post-procedural acute cholangitis occurred in 12.8%of cases (12/94). However, no statistically significant risk factors were identified for cholangitis or biliary tract infection. Peritonitis occurred in only 2.1% of cases (2/94). Univariate analysis, using a 1.5 cm cut-off for the distance between the liver and gastrointestinal tract, revealed significant risk factors: braided-type SEMS, bile duct diameter (especially >4 mm), 6 mm diameter SEMS, and tract dilation ( 0.001, 0.020, =0.023, and =0.046, respectively). Adjusting the cut-offs to 2 cm underscored braided-type SEMS and tract dilation as risk factors ( =0.002 and =0.046, respectively). With 2.5-cm cut-offs, only braided-type SEMS remained significant ( =0.018). Mortality within 14 and 30 days following EUS-HGS was 5.3% (5/94) and 16.0% (15/94), respectively. EUS-HGS using SEMS demonstrated high technical and clinical success rates. Laser-cut SEMS may be superior in preventing early AEs.
PubMed: 38292592
DOI: 10.1055/a-2240-1100 -
International Journal of Molecular... Jan 2024Respiratory diseases in ruminants are a main cause of economic losses to farmers worldwide. Approximately 25% of ruminants experience at least one episode of respiratory...
Respiratory diseases in ruminants are a main cause of economic losses to farmers worldwide. Approximately 25% of ruminants experience at least one episode of respiratory disease during the first year of life. is the main etiological bacterial agent in the ruminant respiratory disease complex. can secrete several virulence factors, such as leukotoxin, lipopolysaccharide, and proteases, that can be targeted to treat infections. At present, little information has been reported on the secretion of A2 proteases and their host protein targets. Here, we obtained evidence that A2 proteases promote the degradation of hemoglobin, holo-lactoferrin, albumin, and fibrinogen. Additionally, we performed biochemical characterization for a specific 110 kDa Zn-dependent metalloprotease (110-Mh metalloprotease). This metalloprotease was purified through ion exchange chromatography and characterized using denaturing and chaotropic agents and through zymography assays. Furthermore, mass spectrometry identification and 3D modeling were performed. Then, antibodies against the 110 kDa-Mh metalloprotease were produced, which achieved great inhibition of proteolytic activity. Finally, the antibodies were used to perform immunohistochemical tests on postmortem lung samples from sheep with suggestive histology data of pneumonic mannheimiosis. Taken together, our results strongly suggest that the 110-Mh metalloprotease participates as a virulence mechanism that promotes damage to host tissues.
Topics: Cattle; Sheep; Animals; Mannheimia haemolytica; Pasteurellosis, Pneumonic; Metalloproteases; Peptide Hydrolases; Ruminants; Collagenases; Zinc; Sheep Diseases
PubMed: 38279292
DOI: 10.3390/ijms25021289 -
Viruses Dec 2023Enterovirus A71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus B3 (CVB3) are pathogenic members of the family that cause a range of diseases, including severe...
Enterovirus A71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus B3 (CVB3) are pathogenic members of the family that cause a range of diseases, including severe central nervous system complications, myocarditis, and pancreatitis. Despite the considerable public health impact of these viruses, no approved antiviral treatments are currently available. In the present study, we confirmed the potential of saucerneol, a compound derived from , as an antiviral agent against EV71, CVA16, and CVB3. In the in vivo model, saucerneol effectively suppressed CVB3 replication in the pancreas and alleviated virus-induced pancreatitis. The antiviral activity of saucerneol is associated with increased mitochondrial ROS (mROS) production. In vitro inhibition of mROS generation diminishes the antiviral efficacy of saucerneol. Moreover, saucerneol treatment enhanced the phosphorylation of STING, TBK-1, and IRF3 in EV71- and CVA16-infected cells, indicating that its antiviral effects were mediated through the STING/TBK-1/IRF3 antiviral pathway, which was activated by increased mROS production. Saucerneol is a promising natural antiviral agent against EV71, CVA16, and CVB3 and has potential against virus-induced pancreatitis and myocarditis. Further studies are required to assess its safety and efficacy, which is essential for the development of effective antiviral strategies against these viruses.
Topics: Humans; Enterovirus; Reactive Oxygen Species; Enterovirus A, Human; Myocarditis; Enterovirus Infections; Antigens, Viral; Antiviral Agents; Pancreatitis; Saururaceae; Interferon Regulatory Factor-3
PubMed: 38275951
DOI: 10.3390/v16010016 -
Viruses Dec 2023(1) Background: Vulnerable populations including transplant recipients are jeopardised by COVID-19. Herein, we report on B and T cell responses among liver and kidney...
(1) Background: Vulnerable populations including transplant recipients are jeopardised by COVID-19. Herein, we report on B and T cell responses among liver and kidney organ recipients at our centre. (2) Methods: 23 liver and 45 kidney (14 thereof combined kidney/pancreas) transplanted patients were vaccinated with two doses of BNT162b2 followed by a booster dose of mRNA-1273 in 28 non-responders 4 months thereafter. Anti-SARS-CoV-2-Ig was measured by specific ELISA and virus neutralisation assay; T cell responses were measured by a spike protein-specific IFN-γ release assay. (3) Results: Compared to controls, B and T cell responses were weak in transplant recipients, particularly in those without prior exposure to SARS-CoV-2. Within this group, only 15% after the first and 58.3% after the second vaccination achieved seroconversion. A total of 14 out of 28 vaccination non-responders achieved a seroconversion after a third dose. Vaccination side effects were more frequent in healthy controls. The use of mycophenolate was associated with reduced anti-SARS-CoV-2-Ig production. (4) Conclusions: Our data confirm that vaccination responses are insufficient after standard vaccination in liver and kidney transplant recipients and are affected to a variable degree by specific immunosuppressants, particularly mycophenolate. Monitoring vaccination success and re-vaccinating those who are unresponsive seems prudent to achieve sufficient titres. Overall, prospective large-scale, multinational, multicentre studies or high-quality meta-analyses will be needed to generate personalised vaccination strategies in order to achieve protective immunity in high-risk, hard-to-immunize populations.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; BNT162 Vaccine; Liver Transplantation; Prospective Studies; T-Lymphocytes; Kidney; Vaccination; Immunosuppressive Agents; Transplant Recipients; Antibodies, Viral
PubMed: 38275936
DOI: 10.3390/v16010001 -
Biomolecules Dec 2023Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar... (Review)
Review
Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar cells. Secondary infection and sepsis are independent prognosticators for AP progression and increased mortality. Accumulating anatomical and epidemiological evidence suggests that the dysbiosis of gut microbiota affects the etiology and severity of AP through intestinal barrier disruption, local or systemic inflammatory response, bacterial translocation, and the regulatory role of microbial metabolites in AP patients and animal models. Recent studies discussing the interactions between gut microbiota and the pancreas have opened new scopes for AP, and new therapeutic interventions that target the bacteria community have received substantial attention. This review concentrates on the alterations of gut microbiota and its roles in modulating gut-pancreas axis in AP. The potential therapies of targeting microbes as well as the major challenges of applying those interventions are explored. We expect to understand the roles of microbes in AP diagnosis and treatment.
Topics: Animals; Humans; Pancreatitis; Acute Disease; Pancreas; Microbiota; Gastrointestinal Microbiome
PubMed: 38254659
DOI: 10.3390/biom14010059 -
Antiviral Research Feb 2024Coxsackievirus B3 (CVB3) is a non-enveloped, single-stranded, positive RNA virus known for its role in provoking inflammatory diseases that affect the heart, pancreas,...
Coxsackievirus B3 (CVB3) is a non-enveloped, single-stranded, positive RNA virus known for its role in provoking inflammatory diseases that affect the heart, pancreas, and brain, leading to conditions such as myocarditis, pancreatitis, and meningitis. Currently, there are no FDA-approved drugs treating CVB3 infection; therefore, identifying potential molecular targets for antiviral drug development is imperative. In this study, we examined the possibility of activating the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that triggers a type-I interferon (IFN) response, in inhibiting CVB3 infection. We found that activation of the cGAS-STING pathway through the application of cGAS (poly dA:dT and herring testes DNA) or STING agonists (2'3'-cGAMP and diamidobenzimidazole), or the overexpression of STING, significantly suppresses CVB3 replication. Conversely, gene-silencing of STING enhances viral replication. Mechanistically, we demonstrated that cGAS-STING activation combats CVB3 infection by inducing IFN response. Notably, we discovered that knockdown of IFN-α/β receptor, a key membrane receptor in type-I IFN signaling, or inhibition of the downstream JAK1/2 signaling with ruxolitinib, mitigates the effects of STING activation, resulting in increased viral protein production. Furthermore, we investigated the interplay between CVB3 and the cGAS-STING pathway. We showed that CVB3 does not trigger cGAS-STING activation; instead, it antagonizes STING and the downstream TBK1 activation induced by cGAMP. In summary, our results provide insights into the interaction of an RNA virus and the DNA-sensing pathway, highlighting the potential for agonist activation of the cGAS-STING pathway in the development of anti-CVB3 drugs.
Topics: Immunity, Innate; Signal Transduction; Nucleotidyltransferases; Interferon Type I; DNA
PubMed: 38242503
DOI: 10.1016/j.antiviral.2024.105811 -
Frontiers in Immunology 2023Type 1 diabetes (T1D) is caused by an autoimmune process which culminates in the destruction of insulin-producing beta cells in the pancreas. It is widely believed that... (Review)
Review
Type 1 diabetes (T1D) is caused by an autoimmune process which culminates in the destruction of insulin-producing beta cells in the pancreas. It is widely believed that a complex and multifactorial interplay between genetic and environmental factors, such as viruses, play a crucial role in the development of the disease. Research over the past few decades has shown that there is not one single viral culprit, nor one single genetic pathway, causing the disease. Rather, viral infections, most notably enteroviruses (EV), appear to accelerate the autoimmune process leading to T1D and are often seen as a precipitator of clinical diagnosis. In support of this hypothesis, the use of anti-viral drugs has recently shown efficacy in preserving beta cell function after onset of diabetes. In this review, we will discuss the various pathways that viral infections utilize to accelerate the development of T1D. There are three key mechanisms linking viral infections to beta-cell death: One is modulated by the direct infection of islets by viruses, resulting in their impaired function, another occurs in a more indirect fashion, by modulating the immune system, and the third is caused by heightened stress on the beta-cell by interferon-mediated increase of insulin resistance. The first two aspects are surprisingly difficult to study, in the case of the former, because there are still many questions about how viruses might persist for longer time periods. In the latter, indirect/immune case, viruses might impact immunity as a hit-and-run scenario, meaning that many or all direct viral footprints quickly vanish, while changes imprinted upon the immune system and the anti-islet autoimmune response persist. Given the fact that viruses are often associated with the precipitation of clinical autoimmunity, there are concerns regarding the impact of the recent global coronavirus-2019 (COVID-19) pandemic on the development of autoimmune disease. The long-term effects of COVID-19 infection on T1D will therefore be discussed, including the increased development of new cases of T1D. Understanding the interplay between viral infections and autoimmunity is crucial for advancing our knowledge in this field and developing targeted therapeutic interventions. In this review we will examine the intricate relationship between viral infections and autoimmunity and discuss potential considerations for prevention and treatment strategies.
Topics: Humans; Diabetes Mellitus, Type 1; Pancreas; Enterovirus Infections; Virus Diseases; Coronavirus Infections; COVID-19
PubMed: 38239343
DOI: 10.3389/fimmu.2023.1326711 -
Preventive Veterinary Medicine Mar 2024Pancreas Disease (PD) is a viral disease that affects Atlantic salmon (Salmo salar) in Norwegian, Scottish and Irish aquaculture. It is caused by salmonid alphavirus...
Pancreas Disease (PD) is a viral disease that affects Atlantic salmon (Salmo salar) in Norwegian, Scottish and Irish aquaculture. It is caused by salmonid alphavirus (SAV) and represents a significant problem in salmonid farming. Infection with SAV leads to reduced growth, mortality, product downgrading, and has a significant financial impact for the farms. The overall aim of this study is to evaluate the effect of various factors on the transmission of SAV and to create a predictive model capable of providing an early warning system for salmon farms within the Norwegian waters. Using a combination of publicly available databases, specifically BarentsWatch, and privately held PCR analyses a feature set consisting of 11 unique features was created based on the input parameters of the databases. An ensemble model was developed based on this feature set using XG-Boost, Ada-Boost, Random Forest and a Multilayer Perceptron. It was possible to successfully predict SAV transmission with 94.4% accuracy. Moreover, it was possible to predict SAV transmission 8 weeks in advance of a 'PD registration' at individual aquaculture salmon farming sites. Important predictors included well boat movement, environmental factors, proximity to sites with a 'PD registration' and seasonality.
Topics: Animals; Alphavirus; Alphavirus Infections; Salmonidae; Aquaculture; Pancreatic Diseases; Fish Diseases; Salmo salar
PubMed: 38232517
DOI: 10.1016/j.prevetmed.2023.106095