Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential.

α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function.

New Therapeutics for Heart Failure Worsening: Focus on Vericiguat.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs.

Pharmacological blockade of 2-AG degradation ameliorates clinical, neuroinflammatory and synaptic alterations in experimental autoimmune encephalomyelitis.

The endocannabinoid system (ECS) is critically involved in the pathophysiology of Multiple Sclerosis (MS), a neuroinflammatory and neurodegenerative disease of the central nervous system (CNS). Over the past decade, researchers have extensively studied the neuroprotective and anti-inflammatory effects of the ECS. Inhibiting the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) has emerged as a promising strategy to mitigate brain damage in MS.

Doxorubicin-Induced Cardiac Senescence Is Alleviated Following Treatment with Combined Polyphenols and Micronutrients through Enhancement in Mitophagy.

Oxidative stress and impaired mitophagy are the hallmarks of cardiomyocyte senescence. Specifically, a decrease in mitophagic flux leads to the accumulation of damaged mitochondria and the development of senescence through increased ROS and other mediators. In this study, we describe the preventive role of A5, a mix of polyphenols and other micronutrients, in doxorubicin (DOXO)-induced senescence of H9C2 cells.

The virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate.

In this paper, we demonstrated that apyrase is released within the host cell cytoplasm during infection to target the intracellular ATP pool. By degrading intracellular ATP, apyrase contributes to prevent caspases activation, thereby inhibiting the activation of pyroptosis in infected cells. Our results show, for the first time, that apyrase is involved in the modulation of host cell survival, thereby aiding this pathogen to dampen the inflammatory response.

Very-low-calorie ketogenic diet vs hypocaloric balanced diet in the prevention of high-frequency episodic migraine: the EMIKETO randomized, controlled trial.

Background: Migraine is the second world's cause of disability. Among non-pharmacological treatments, nutritional intervention, particularly ketogenic diet, represents one of the most promising approaches.

Methods: This a prospective, single center, randomized, controlled study aimed at evaluating the efficacy of a very low-calorie ketogenic diet (VLCKD) compared to a hypocaloric balanced diet (HBD) in migraine prophylaxis in patients affected by high-frequency episodic migraine (HFEM) with a Body Mass Index (BMI) > 27 kg/m.

SIRT5 Activation and Inorganic Phosphate Binding Reduce Cancer Cell Vitality by Modulating Autophagy/Mitophagy and ROS.

Cancer cells show increased glutamine consumption. The glutaminase (GLS) enzyme controls a limiting step in glutamine catabolism. Breast tumors, especially the triple-negative subtype, have a high expression of GLS.

Prolonged clinical remission of type 1 diabetes sustained by calcifediol and low-dose basal insulin: a case report.

Herein, we describe an unusually prolonged duration (31 months) of the clinical remission phase in a 22-year-old Italian man with new-onset type 1 diabetes. Shortly after the disease diagnosis, the patient was treated with calcifediol (also known as 25-hydroxyvitamin D3 or calcidiol), coupled with low-dose basal insulin, to correct hypovitaminosis D and to exploit the anti-inflammatory and immunomodulatory properties of vitamin D. During the follow-up period, the patient retained a substantial residual β-cell function and remained within the clinical remission phase, as evidenced by an insulin dose-adjusted glycated hemoglobin value <9.

An Observational Study on Chronic Pain Biomarkers in Fibromyalgia and Osteoarthritis Patients: Which Role for Mu Opioid Receptor's Expression on NK Cells?

The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. Here, we investigate the role of MLM on natural killer (NK) cells in the same patients.

Role of SIRT3 in Microgravity Response: A New Player in Muscle Tissue Recovery.

Life on Earth has evolved in the presence of a gravity constraint. Any change in the value of such a constraint has important physiological effects. Gravity reduction (microgravity) alters the performance of muscle, bone and, immune systems among others.

Nicotine in Combination with SARS-CoV-2 Affects Cells Viability, Inflammatory Response and Ultrastructural Integrity.

The aims of our study are to: (i) investigate the ability of nicotine to modulate the expression level of inflammatory cytokines in A549 cells infected with SARS-CoV-2; (ii) elucidate the ultrastructural features caused by the combination nicotine+SARS-CoV-2; and (iii) demonstrate the mechanism of action. In this study, A549 cells pretreated with nicotine were either exposed to LPS or poly(I:C), or infected with SARS-CoV-2. Treated and untreated cells were analyzed for cytokine production, cytotoxicity, and ultrastructural modifications.

BNT162b2 mRNA COVID-19 Vaccine Does Not Impact the Honeymoon Phase in Type 1 Diabetes: A Case Report.

Type 1 diabetes (T1D), which is caused by the autoimmune destruction of insulin-secreting pancreatic beta cells, represents a high-risk category requiring COVID-19 vaccine prioritization. Although COVID-19 vaccination can lead to transient hyperglycemia (vaccination-induced hyperglycemia; ViHG), its influence on the course of the clinical remission phase of T1D (a.k.

DNA damage in dementia: Evidence from patients affected by severe Chronic Obstructive Pulmonary Disease (COPD) and meta-analysis of most recent literature.

Oxidative stress that leads to oxidatively damaged DNA, plays a crucial role in chronic obstructive pulmonary disease (COPD) as well as in the onset of neurodegenerative diseases. The consequent genomic instability is the first neuropathological event found in the preclinical phase of cognitive impairment (CI), and the level of DNA damage is closely related to the degree of dementia. Since CI has been associated with COPD, we investigated the extent of DNA damage in isolated lymphocytes with the Comet assay, in a group of severe COPD patients with cognitive function measured by the Mini-Mental State Examination (MMSE).

Preventive Measures against Pandemics from the Beginning of Civilization to Nowadays-How Everything Has Remained the Same over the Millennia.

As of 27 March 2022, the β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 487 million individuals worldwide, causing more than 6.14 million deaths. SARS-CoV-2 spreads through close contact, causing the coronavirus disease 2019 (COVID-19); thus, emergency lockdowns have been implemented worldwide to avoid its spread.

Long Lasting Cellular Immune Response Induced by mRNA Vaccination: Implication for Prevention Strategies.

As the COVID19 pandemic continues to spread and vaccinations are administered throughout the world at different rates and with different strategies, understanding the multiple aspects of the immune response to vaccinations is required to define more efficient vaccination strategies. To date, the duration of protection induced by COVID19 vaccines is still matter of debate. To assess whether 2-doses vaccination with BNT162b2 mRNA COVID-19 vaccine was sufficient to induce a persistent specific cellular immune response, we evaluated the presence of SARS-COV2 Spike-specific B and T lymphocytes in 28 healthcare workers 1 and 7 months after completing the vaccination cycle.

Daily Vegetables Intake and Response to COPD Rehabilitation. The Role of Oxidative Stress, Inflammation and DNA Damage.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to reduce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and reduction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD.

The Interplay between Chronic Pain, Opioids, and the Immune System.

Chronic pain represents one of the most serious worldwide medical problems, in terms of both social and economic costs, often causing severe and intractable physical and psychological suffering. The lack of biological markers for pain, which could assist in forming clearer diagnoses and prognoses, makes chronic pain therapy particularly arduous and sometimes harmful. Opioids are used worldwide to treat chronic pain conditions, but there is still an ambiguous and inadequate understanding about their therapeutic use, mostly because of their dual effect in acutely reducing pain and inducing, at the same time, tolerance, dependence, and a risk for opioid use disorder.

Central Modulation of Selective Sphingosine-1-Phosphate Receptor 1 Ameliorates Experimental Multiple Sclerosis.

Future treatments of multiple sclerosis (MS), a chronic autoimmune neurodegenerative disease of the central nervous system (CNS), aim for simultaneous early targeting of peripheral immune function and neuroinflammation. Sphingosine-1-phosphate (S1P) receptor modulators are among the most promising drugs with both "immunological" and "non-immunological" actions. Selective S1P receptor modulators have been recently approved for MS and shown clinical efficacy in its mouse model, the experimental autoimmune encephalomyelitis (EAE).

Altered Tregs Differentiation and Impaired Autophagy Correlate to Atherosclerotic Disease.

Atherosclerosis is a progressive vascular disease representing the primary cause of morbidity and mortality in developed countries. Formerly, atherosclerosis was considered as a mere passive accumulation of lipids in blood vessels. However, it is now clear that atherosclerosis is a complex and multifactorial disease, in which the involvement of immune cells and inflammation play a key role.

Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases.

Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane.

Biomarkers of DNA damage in COPD patients undergoing pulmonary rehabilitation: Integrating clinical parameters with genomic profiling.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by severe respiratory symptoms. COPD shows several hallmarks of aging, and an increased oxidative stress, which is responsible for different clinical and molecular COPD features, including an increased frequency of DNA damage. The current pharmacological treatment options for COPD are mostly symptomatic, and generally do not influence disease progression and survival.

Modulating the metabolism by trimetazidine enhances myoblast differentiation and promotes myogenesis in cachectic tumor-bearing c26 mice.

Trimetazidine (TMZ) is a metabolic reprogramming agent able to partially inhibit mitochondrial free fatty acid β-oxidation while enhancing glucose oxidation. Here we have found that the metabolic shift driven by TMZ enhances the myogenic potential of skeletal muscle progenitor cells leading to MyoD, Myogenin, Desmin and the slow isoforms of troponin C and I over-expression. Moreover, similarly to exercise, TMZ stimulates the phosphorylation of the AMP-activated protein kinase (AMPK) and up-regulates the peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α), both of which are known to enhance the mitochondrial biogenesis necessary for myoblast differentiation.

CXCL12 prolongs naive CD4+ T lymphocytes survival via activation of PKA, CREB and Bcl2 and BclXl up-regulation.

Background: Naive T lymphocytes recirculate through the body, traveling from secondary lymphoid organs through tissues and via lymphatic vessels and peripheral blood into other secondary lymphoid organs and into the bone marrow. In these tissues, lymphocytes are exposed to the chemokine CXCL12 which is abundantly produced in bone marrow and in lymph nodes by stromal cells. CXCL12 is known to drive lymphocytes chemotaxis and, in cells types such as stem cells, an antiapopototic effect has been described.

Variation in interferon sensitivity and induction between Usutu and West Nile (lineages 1 and 2) viruses.

Given the pivotal role of monocyte-derived dendritic cells (DCs) in determining the magnitude of the antiviral innate immune response, we sought to determine whether Usutu virus (USUV) and West Nile virus (WNV) lineages (L)1 and L2 can infect DCs and affect the rate of type I interferon (IFN) activation. The sensitivity of these viruses to types I and III IFNs was also compared. We found that USUV can infect DCs, induce higher antiviral activities, IFN alpha subtypes and the IFN stimulated gene (ISG)15 pathway, and is more sensitive to types I and III IFNs than WNVs.