Effects of CRAMP on the gut-brain axis in experimental sepsis.

The collaboration between the microbiota, mucosa, and intestinal epithelium is crucial for defending against pathogens and external antigens. Dysbiosis disrupts this balance, allowing pathogens to thrive and potentially enter the bloodstream, triggering immune dysregulation and potentially leading to sepsis. Antimicrobial peptides like LL-37 and CRAMP are pivotal in innate immune defense.

Antimicrobial peptides and other potential biomarkers of critical illness in SARS-CoV-2 patients with acute kidney injury. AMPAKI-CoV study.

Antimicrobial peptides (AMPs) constitute a complex network of 10-100 amino acid sequence molecules widely distributed in nature. While over 300 AMPs have been described in mammals, cathelicidins and defensins remain the most extensively studied. Some publications have explored the role of AMPs in COVID-19, but these findings are preliminary, and in vivo studies are still lacking.

Transcriptome analysis of six tissues obtained post-mortem from sepsis patients.

Septic shock is a life-threatening clinical condition characterized by a robust immune inflammatory response to disseminated infection. Little is known about its impact on the transcriptome of distinct human tissues. To address this, we performed RNA sequencing of samples from the prefrontal cortex, hippocampus, heart, lung, kidney and colon of seven individuals who succumbed to sepsis and seven uninfected controls.

Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury.

Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity.

Antimicrobial peptides in the gut-brain axis: A straightforward review to unravel some missing links.

Antimicrobial peptides (AMPs) are intriguing molecules, able to directly kill several microorganisms and to regulate multiple aspects of the immune response. Despite the extensive studies on the role of AMPs in the epithelial barrier, placing them as a pivotal line of defense against pathogen invasion, little attention has been directed to their role in the maintenance and modulation of the gut microbiota and, by consequence, of the homeostasis of extra intestinal tissues. Here, we review the recent literature about the microbiome-gut-brain axis, focusing on the role of AMPs in this scenario.

Long-term efficacy of gliflozins versus gliptins for Type 2 Diabetes after metformin failure: a systematic review and network meta-analysis.

After metformin failure in treatment for diabetes type 2, there is no trivial option for adjuvant medication. The last two oral class medications, gliflozins and gliptins, have different mechanisms of action but have never been compared in long run studies. The aim of the present meta-analysis is to assess the overall long-term efficacy of these drugs after metformin failure.

Local and systemic effects of aging on acute pancreatitis.

Background: /Objectives: Evaluation of the local and systemic effects of aging on the severity of acute pancreatitis (AP) in an experimental rat model in elderly animals.

Methods: AP was induced in Wistar rats by intraductal 2.5% taurocholate injection and divided into two groups: Young (3 month old) and Aged (18 month old).

CD89 Is a Potent Innate Receptor for Bacteria and Mediates Host Protection from Sepsis.

Direct bacterial recognition by innate receptors is crucial for bacterial clearance. Here, we show that the IgA receptor CD89 is a major innate receptor that directly binds bacteria independently of its cognate ligands IgA and c-reactive protein (CRP). This binding is only partially inhibited by serum IgA and induces bacterial phagocytosis by CD11c dendritic cells and monocytes and/or macrophages, suggesting a physiological role in innate host defense.

Short-Term Effects of Sepsis and the Impact of Aging on the Transcriptional Profile of Different Brain Regions.

Among the clinical manifestations observed in septic patients, sepsis-associated encephalopathy (SAE) is probably the most obscure and poorly explored. It is well established, however, that SAE is more prevalent in aged individuals and related to a worse outcome. In this context, we decided to investigate the acute effects of sepsis, induced by cecal ligation and puncture (CLP), on the cerebral transcriptional profile of young and old rats.

Diazoxide reduces local and remote organ damage in a rat model of intestinal ischemia reperfusion.

Background: Intestinal ischemia reperfusion is a common clinical condition that causes functional impairment. Once tight junctions are damaged, barrier function is compromised, and the intestines become a source for entry of bacterial and inflammatory mediators into the circulation, leading to systemic inflammatory response syndrome, multiple organ failure, and death. It is possible that diazoxide could protect the intestines against ischemia reperfusion.

Reduction of venous pressure during the resection of liver metastases compromises enteric blood flow: IGFBP-1 as a novel biomarker of intestinal barrier injury.

Objectives: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage.

Methods: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection.

Septic Shock and the Aging Process: A Molecular Comparison.

Aging is a continuous process promoted by both intrinsic and extrinsic factors that each trigger a multitude of molecular events. Increasing evidence supports a central role for inflammation in this progression. Here, we discuss how the low-grade chronic inflammation that characterizes aging is tightly interconnected with other important aspects of this process, such as DNA damage, mitochondrial dysfunction, and epigenetic changes.

Animal models of neuroinflammation secondary to acute insults originated outside the brain.

The term "neuroinflammation" has been widely used to describe a series of acute or chronic conditions that cause inflammation in the central nervous system (CNS). Neurological damage can be a consequence of direct local injury or, secondary, of systemic or even distant inflammatory processes. In this respect, animal models have been developed to better understand the pathophysiology and, possibly, to evaluate more effective methods of treatment for these disorders.

Cathelicidin-deficient mice exhibit increased survival and upregulation of key inflammatory response genes following cecal ligation and puncture.

Unlabelled: Antimicrobial peptides possess a myriad of molecular properties including bacterial killing and the regulation of many aspects of innate immunity. Cathelicidins are a group of antimicrobial peptides widely investigated by the scientific community. Many studies have focused on the bactericidal and pro-inflammatory roles of cathelicidins.

Insights into the Function of Long Noncoding RNAs in Sepsis Revealed by Gene Co-Expression Network Analysis.

Sepsis is a major cause of death and its incidence and mortality increase exponentially with age. Most gene expression studies in sepsis have focused in protein-coding genes and the expression patterns, and potential roles of long noncoding RNAs (lncRNAs) have not been investigated yet. In this study, we performed co-expression network analysis of protein-coding and lncRNAs measured in neutrophil granulocytes from adult and elderly septic patients, along with age-matched healthy controls.

The dual role of cathelicidins in systemic inflammation.

Antimicrobial peptides are key components of the innate immune system. They act as broad-spectrum antimicrobial agents against Gram-positive and -negative bacteria, viruses, and fungi. More recently, antimicrobial peptides have been ascribed immunomodulatory functions, including roles in wound healing, induction of cytokines, and altering host gene expression.

Antimicrobial peptide LL-37 participates in the transcriptional regulation of melanoma cells.

Antimicrobial peptides are an ancient family of molecules that emerged millions of years ago and have been strongly conserved during the evolutionary process of living organisms. Recently, our group described that the human antimicrobial peptide LL-37 migrates to the nucleus, raising the possibility that LL-37 could directly modulate transcription under certain conditions. Here, we showed evidence that LL-37 binds to gene promoter regions, and LL-37 gene silencing changed the transcriptional program of melanoma A375 cells genes associated with histone, metabolism, cellular stress, ubiquitination and mitochondria.

Sepsis induces telomere shortening: a potential mechanism responsible for delayed pathophysiological events in sepsis survivors?

Sepsis survivors suffer from additional morbidities, including higher disk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening.

Proteomic profiling identifies N-acetylmuramoyl-l-alanine amidase as a novel biomarker of sepsis.

Aim: Sepsis is a critical condition that leads to high mortality and is the most common cause of death in intensive care units. Despite exhaustive efforts by the scientific community, a reliable biomarker for diagnosis, evolution and prognosis of sepsis is still lacking. Results & methodology: Here, using high-throughput proteomics, we describe N-acetylmuramoyl-l-alanine amidase as a novel candidate for differentiating infectious and noninfectious inflammatory syndromes.

Intestinal Barrier Dysfunction in Human Pathology and Aging.

Background: The intestinal barrier is a layer that constitutes the most important barrier against the external environment. It can be partially disrupted in several frequent scenarios, leading to autoimmune and inflammatory diseases. Translocation of intestinal luminal contents into the intestinal mucosa may induce inflammatory disorders and therefore tissue injuries.

Negative regulation of bacterial killing and inflammation by two novel CD16 ligands.

Sepsis, a leading cause of death worldwide, involves exacerbated proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here, we used a phage display library to identify two peptides in Escherichia coli that interact with host innate receptors.

"Neuropeptides in the brain defense against distant organ damage".

Delirium, or acute confusional state, is a common manifestation in diseases that originate outside the central nervous system, affecting 30-40% of elderly hospitalized patients and up to 80% of the critically ill, even though it remains unclear if severe systemic inflammation is able or not to induce cellular disturbances and immune activation in the brain. Neuropeptides are pleotropic molecules heterogeneously distributed throughout the brain and possess a wide spectrum of functions, including regulation of the inflammatory response, so we hypothesized that they would be the major alarm system in the brain before overt microglia activation. In order to investigate this hypothesis, we induced acute pancreatitis in 8-10week old rats and collected brain tissue, 12 and 24h following pancreatic injury, to measure neuropeptide and cytokine tissue levels.

Intestinal barrier dysfunction and increased COX-2 gene expression in the gut of elderly rats with acute pancreatitis.

Background/objectives: The clinical course of acute pancreatitis can vary from mild to severe. In its most severe manifestation, acute pancreatitis is associated with an exacerbated systemic inflammatory response and high mortality rates. The severe form of acute pancreatitis is more frequent in elderly patients than in young patients, but the mechanisms underlying this difference are still under investigation.