Extracellular vesicles as human therapeutics: A scoping review of the literature.

Extracellular vesicles (EVs) are released by all cells and contribute to cell-to-cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested.

Immunobiology of pregnancy: from basic science to translational medicine.

Embryo implantation failure and spontaneous abortions represent the main causes of infertility in developed countries. Unfortunately, incomplete knowledge of the multiple factors involved in implantation and fetal development keeps the success rate of medically assisted procreation techniques relatively low. According to recent literature, cellular and molecular mechanisms of 'immunogenic tolerance' towards the embryo are crucial to establish an 'anti-inflammatory' state permissive of a healthy pregnancy.

Caloric restriction for the immunometabolic control of human health.

Nutrition affects all physiological processes occurring in our body, including those related to the function of the immune system; indeed, metabolism has been closely associated with the differentiation and activity of both innate and adaptive immune cells. While excessive energy intake and adiposity have been demonstrated to cause systemic inflammation, several clinical and experimental evidence show that calorie restriction (CR), not leading to malnutrition, is able to delay aging and exert potent anti-inflammatory effects in different pathological conditions. This review provides an overview of the ability of different CR-related nutritional strategies to control autoimmune, cardiovascular, and infectious diseases, as tested by preclinical studies and human clinical trials, with a specific focus on the immunological aspects of these interventions.

Regulatory T cells as metabolic sensors.

Compelling experimental evidence links immunity and metabolism. In this perspective, we propose forkhead-box-P3 (FoxP3)CD4CD25 regulatory T (Treg) cells as key metabolic sensors controlling the immunological state in response to their intrinsic capacity to perceive nutritional changes. Treg cell high anabolic state in vivo, residency in metabolically crucial districts, and recirculation between lymphoid and non-lymphoid sites enable them to recognize the metabolic cues and adapt their intracellular metabolism and anti-inflammatory function at the paracrine and systemic levels.

Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms.

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories.

Epigenetics: An opportunity to shape innate and adaptive immune responses.

Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post-translational modifications and the regulation of chromatin accessibility by non-coding RNAs, all of which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental-driven nature, piloting myeloid and lymphoid cell fate decisions with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage-specific transcription factors and maintenance of cell type-specific epigenetic modifications, referred to as 'epigenetic memory', dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells.

A rapid and inexpensive genotyping method using dried blood spots for mutational analysis in a mutant mouse model: an update.

Background: Dried blood spot (DBS) testing is a well-known method of bio-sampling by which blood samples are blotted and dried on filter paper. The dried samples can then be analyzed by several techniques such as DNA amplification and HPLC. We have developed a non-invasive sampling followed by an alternative protocol for genomic DNA extraction from a drop of blood adsorbed on paper support.

High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease.

Aims/hypothesis: We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time.

Methods: Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5 years after diabetes onset.

Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (i) reduce cardiovascular and renal events in patients with and without type 2 diabetes (T2D). However, the underlying mechanisms are debated. Low-grade inflammation (LGI) is a key driver of vascular complications, suggested to be attenuated by SGLT-2i in animal models.

The folate way to T cell fate.

The role of folate-dependent one carbon (1C) metabolism in CD4 T cell polarization is incompletely understood. In this issue of Immunity, Sugiura et al. (2021) provide evidence that blocking the 1C metabolic enzyme MTHFD2 may curb pro-inflammatory CD4 T cells, while redirecting them toward a regulatory T cell phenotype.

CD4 T-Cell Activation Prompts Suppressive Function by Extracellular Vesicle-Associated MicroRNAs.

MicroRNAs (miRNAs), small non-coding molecules targeting messenger RNAs and inhibiting protein translation, modulate key biological processes, including cell growth and development, energy utilization, and homeostasis. In particular, miRNAs control the differentiation, survival, and activation of CD4 T conventional (Tconv) cells, key players of the adaptive immunity, and regulate the physiological response to infections and the pathological loss of immune homeostasis in autoimmunity. Upon T-cell receptor (TCR) stimulation, the described global miRNA quantitative decrease occurring in T cells is believed to promote the acquisition of effector functions by relaxing the post-transcriptional repression of genes associated with proliferation and cell activity.

Type 1 Diabetes and Associated Cardiovascular Damage: Contribution of Extracellular Vesicles in Tissue Crosstalk.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of the insulin secreting β-cells, with consequent aberrant blood glucose levels. Hyperglycemia is the common denominator for most of the chronic diabetic vascular complications, which represent the main cause of life reduction in T1D patients. For this disease, three interlaced medical needs remain: understanding the underlying mechanisms involved in pancreatic β-cell loss; identifying biomarkers able to predict T1D progression and its related complications; recognizing novel therapeutic targets.

Effect of time and titer in convalescent plasma therapy for COVID-19.

The clinical benefit of convalescent plasma (CP) for patients with coronavirus disease (COVID)-19 is still debated. In this systematic review and meta-analysis, we selected 10 randomized clinical trials (RCTs) and 15 non-randomized studies (total number of patients = 22,591) of CP treatment and evaluated two different scenarios: (1) disease stage of plasma recipients and (2) donated plasma antibody titer, considering all-cause mortality at the latest follow-up. Our results show that, when provided at early stages of the disease, CP significantly reduced mortality: risk ratio (RR) 0.

Diabetes and kidney disease: emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists.

Kidney disease is a frequent microvascular complication of both type 1 and type 2 diabetes. Historic trials have demonstrated that a tight glycaemic control is the most powerful approach to decrease the chances of developing diabetic nephropathy. However, having an HbA1c < 7% does not completely suppress the risk of kidney disease.

Elevated HbA1c levels in pre-Covid-19 infection increases the risk of mortality: A sistematic review and meta-analysis.

Aims: Diabetes is emerging as a risk factor for coronavirus disease (COVID)-19 prognosis. However, contradictory findings have been reported regarding the impact of glycaemic control on COVID-19 outcome. The aim of this meta-analysis was to explore the impact of hospital pre-admission or at-admission values of HbA1c on COVID-19 mortality or worsening in patients with diabetes.

Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential.

Human CD4CD25FOXP3 regulatory T (Treg) cells are key players in the control of immunological self-tolerance and homeostasis. Here, we report that signals of pseudo-starvation reversed human Treg cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation, metabolism, and transmembrane solute carrier transport. At the molecular level, the Treg cell proliferative response was dependent on the induction of the cystine/glutamate antiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclear factor erythroid 2-related factor 2 (NRF2).

Metabolomics, Lipidomics, and Immunometabolism.

Metabolomics, lipidomics, and the study of cellular metabolism are gaining increasing interest particularly in the field of immunology, since the activation and effector functions of immune cells are profoundly controlled by changes in cellular metabolic asset. Among the different techniques that can be used for the evaluation of cellular metabolism, the Seahorse Extracellular Flux Analyzer allows the real time measurement of both glycolytic and mitochondrial respiration pathways in cells of interest, through the assessment of extracellular acidification and oxygen consumption rate. Metabolomics, on the other hand, is the high-throughput analysis of metabolites, i.

The pleiotropic roles of leptin in metabolism, immunity, and cancer.

The discovery of the archetypal adipocytokine leptin and how it regulates energy homeostasis have represented breakthroughs in our understanding of the endocrine function of the adipose tissue and the biological determinants of human obesity. Investigations on leptin have also been instrumental in identifying physio-pathological connections between metabolic regulation and multiple immunological functions. For example, the description of the promoting activities of leptin on inflammation and cell proliferation have recognized the detrimental effects of leptin in connecting dysmetabolic conditions with cancer and with onset and/or progression of autoimmune disease.

Extracellular vesicle-shuttled miRNAs: a critical appraisal of their potential as nano-diagnostics and nano-therapeutics in type 2 diabetes mellitus and its cardiovascular complications.

Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease causing the development of a large range of cardiovascular (CV) complications. Lifestyle changes and pharmacological therapies only partially halt T2DM progression, and existing drugs are unable to completely suppress the increased CV risk of T2DM patients. Extracellular vesicles (EV)s are membrane-coated nanoparticles released by virtually all living cells and are emerging as novel mediators of T2DM and its CV complications.

Does microRNA Perturbation Control the Mechanisms Linking Obesity and Diabetes? Implications for Cardiovascular Risk.

Metabolic disorders such as obesity and type 2 diabetes (T2D) are considered the major risk factors for the development of cardiovascular diseases (CVD). Although the pathological mechanisms underlying the mutual development of obesity and T2D are difficult to define, a better understanding of the molecular aspects is of utmost importance to identify novel therapeutic targets. Recently, a class of non-coding RNAs, called microRNAs (miRNAs), are emerging as key modulators of metabolic abnormalities.

T Cells: Warriors of SARS-CoV-2 Infection.

Severe infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is characterized by massive cytokine release and T cell loss. The exaggerated host immune response, incapable of viral clearance, instead aggravates respiratory distress, as well as cardiac, and/or damage to other organs. The mortality pattern of SARS-CoV-2 infection, higher in older versus younger adults and almost absent in children, is possibly caused by the effects of age and pre-existing comorbidities on innate and adaptive immunity.

Immunometabolism of regulatory T cells in cancer.

Regulatory T (Treg) cells are known to orchestrate the regulatory mechanisms aimed at suppressing pathological auto-reactive immune responses and are thus key in ensuring the maintenance of immune homeostasis. On the other hand, the presence of Treg cells with enhanced suppressive capability in a plethora of human cancers represents a major obstacle to an effective anti-cancer immune response. A relevant research effort has thus been dedicated to comprehend Treg cell biology, leading to a continuously refining characterization of their phenotype and function and unveiling the central role of metabolism in ensuring Treg cell fitness in cancer.