Marine 5-thiohistidines as protective molecules from skin damage

Introduction Marine environment is a great source of bioactive molecules, whose biological properties and applications are often used especially to prevent skin diseases and aging caused by UVA­exposure. Ovothiols are methyl­5­thiohistidines from marine invertebrates, bacteria, and microalgae, which protect cells from environmental stressors. Recently, we have shown that, ovothiol, isolated from sea urchin eggs, exerts anti­inflammatory and antioxidant activities on human endothelial cells, and exhibits antifibrotic effect in an in vivo model of liver fibrosis.info:eu-repo/semantics/publishedVersio

Antioxidant and immune response of the sea urchin Paracentrotus lividus to different re-suspension patterns of highly polluted marine sediments

Marine pollution due to disused industrial activities is a major threat to ecosystems and human health, for example through the effects of re-suspension of toxic substances that are present in contaminated sediments. Here, we examined the effects of different re-suspension patterns of polluted sediments from the site of national interest Bagnoli-Coroglio, on the immune system of the sea urchin Paracentrotus lividus. An indoor experiment was set up exposing sea urchins for 34 days to such sediments and evaluating the effects of two patterns of water turbulence, mimicking natural storms at sea. One group of animals experienced an “aggregated” pattern of turbulence, consisting in two events, each lasting 2 days, separated by only 3 calm days, while a second group experienced two events of turbulence separated by 17 calm days (spaced pattern). At different times from the beginning of the experiment, coelomic fluid was collected from the animals and immune cells were examined for cell count and morphology, oxidative stress variables, and expression of genes involved in metal detoxification, stress response and inflammation. Our results highlighted that the aggregated pattern of turbulence was more noxious for sea urchins. Indeed, their immune system was altered, over the exposure time, as indicated by the increase of red amoebocytes number. Moreover, despite of an increase of the antioxidant power, animals from this group displayed a very significant ROS over-production at the end of the experiment. Conversely, animals in the spaced condition activated a different immune response, mainly having phagocytes as actors, and were able to partially recover from the received stress at the end of the experiment. No changes in the expression of genes related to antioxidant and anti-inflammatory responses were observed in both groups. By contrast, a down-regulation of various metallothioneins (4, 6, 7 and 8) in the group subjected to aggregated pattern was observed, while metallothionein 8 was up-regulated in the animals from the group exposed to the spaced pattern of turbulence. This work provides the first evidence of how sea urchins can respond to different re-suspension patterns of polluted sediments by modulating their immune system functions. The present data are relevant in relation to the possible environmental restoration of the study site, whose priorities include the assessment of the effects of marine pollution on local organisms, among which P. lividus represents a key benthic species

Appropriate lung management in patients with primary antibody deficiencies

Introduction: Human primary immunodeficiency diseases (PIDs) include a broad spectrum of more than 350 disorders, involving different branches of the immune system and classified as 'rare diseases.' Predominantly antibody deficiencies (PADs) represent more than half of the PIDs diagnosed in Europe and are often diagnosed in the adulthood. Areas covered: Although PAD could first present with autoimmune or neoplastic features, respiratory infections are frequent and respiratory disease represents a relevant cause of morbidity and mortality. Pulmonary complications may be classified as infection-related (acute and chronic), immune-mediated, and neoplastic. Expert opinion: At present, no consensus guidelines are available on how to monitor and manage lung complications in PAD patients. In this review, we will discuss the available diagnostic, prognostic and therapeutic instruments and we will suggest an appropriate and evidence-based approach to lung diseases in primary antibody deficiencies. We will also highlight the possible role of promising new tools and strategies in the management of pulmonary complications. However, future studies are needed to reduce of diagnostic delay of PAD and to better understand lung diseases mechanisms, with the final aim to ameliorate therapeutic options that will have a strong impact on Quality of Life and long-term prognosis of PAD patients

Insights into the light response of skeletonema marinoi: Involvement of ovothiol

Diatoms are one of the most widespread groups of microalgae on Earth. They possess extraordinary metabolic capabilities, including a great ability to adapt to different light conditions. Recently, we have discovered that the diatom Skeletonema marinoi produces the natural antioxidant ovothiol B, until then identified only in clams. In this study, we investigated the light-dependent modulation of ovothiol biosynthesis in S. marinoi. Diatoms were exposed to different light conditions, ranging from prolonged darkness to low or high light, also differing in the velocity of intensity increase (sinusoidal versus square-wave distribution). The expression of the gene encoding the key ovothiol biosynthetic enzyme, ovoA, was upregulated by high sinusoidal light mimicking natural conditions. Under this situation higher levels of reactive oxygen species and nitric oxide as well as ovothiol and glutathione increase were detected. No ovoA modulation was observed under prolonged darkness nor low sinusoidal light. Unnatural conditions such as continuous square-wave light induced a very high oxidative stress leading to a drop in cell growth, without enhancing ovoA gene expression. Only one of the inducible forms of nitric oxide synthase, nos2, was upregulated by light with consequent production of NO under sinusoidal light and darkness conditions. Our data suggest that ovothiol biosynthesis is triggered by a combined light stress caused by natural distribution and increased photon flux density, with no influence from the daily light dose. These results open new perspectives for the biotechnological production of ovothiols, which are receiving a great interest for their biological activities in human model systems

Protocol for the unclassified primary antibody deficiency (unPAD) study:Characterization and classification of patients using the ESID online registry

BACKGROUND: Primary antibody deficiencies (PADs) without an identified monogenetic origin form the largest and most heterogeneous group of primary immunodeficiencies. These patients often remain undiagnosed for years and many present to medical attention in adulthood after several infections risking structural complications. Not much is known about their treatment, comorbidities, or prognosis, nor whether the various immunological forms (decreased total IgG, IgG subclass(es), IgM, IgA, specific antibody responses, alone or in combination(s)) should be considered as separate, clearly definable subgroups. The unclassified primary antibody deficiency (unPAD) study aims to describe in detail all PAD patients without an identified specific monogenetic defect regarding their demographical, clinical, and immunological characteristics at presentation and during follow-up. In constructing these patterns, the unPAD study aims to reduce the number of missed and unidentified PAD patients in the future. In addition, this study will focus on subclassifying unPAD to support the identification of patients at higher risk for infection or immune dysregulation related complications, enabling the development of personalized follow-up and treatment plans. METHODS AND ANALYSIS: We present a protocol for a multicenter observational cohort study using the ESID online Registry. Patients of all ages who have given informed consent for participation in the ESID online Registry and fulfill the ESID Clinical Working Definitions for ‘unclassified antibody deficiency’, ‘deficiency of specific IgG’, ‘IgA with IgG subclass deficiency’, ‘isolated IgG subclass deficiency’, ‘selective IgM deficiency’, ‘selective IgA deficiency’ or ‘common variable immunodeficiency’ will be included. For all patients, basic characteristics can be registered at first registration and yearly thereafter in level 1 forms. Detailed characteristics of the patients can be registered in level 2 forms. Consecutive follow-up forms can be added indefinitely. To ensure the quality of the collected data, all data will be fully monitored before they are exported from the ESID online Registry for analysis. Outcomes will be the clinical and immunological characteristics of unPAD at presentation and during follow-up. Subgroup analyses will be made based on demographical, clinical and immunological characteristics

Sarcoidosis versus Granulomatous and Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency: A Comparative Review

Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches

Decline of gastric cancer mortality in common variable immunodeficiency in the years 2018-2022

Introduction: In patients with Common Variable Immunodeficiency, malignancy has been reported as the leading cause of death in adults, with a high risk of B-cell lymphomas and gastric cancer.Methods: We conducted a five-year prospective study aiming to update the incidence and mortality of gastric cancer and the incidence of gastric precancerous lesions in 512 CVID patients who underwent a total of 400 upper gastrointestinal endoscopies.Results: In the pre-pandemic period, 0.58 endoscopies were performed per patient/year and in the COVID-19 period, 0.39 endoscopies were performed per patient/year. Histology revealed areas with precancerous lesions in about a third of patients. Patients who had more than one gastroscopy during the study period were more likely to have precancerous lesions. Two patients received a diagnosis of gastric cancer in the absence of Helicobacter pylori infection. The overall prevalence of Helicobacter pylori infection in biopsy specimens was 19.8% and related only to active gastritis. Among patients who had repeated gastroscopies, about 20% progressed to precancerous lesions, mostly independent of Helicobacter pylori.Discussion: While gastric cancer accounted for one in five deaths from CVID in our previous survey, no gastric cancer deaths were recorded in the past five years, likely consistent with the decline in stomach cancer mortality observed in the general population. However, during the COVID-19 pandemic, cancer screening has been delayed. Whether such a delay or true decline could be the reason for the lack of gastric cancer detection seen in CVID may become clear in the coming years. Due to the high incidence of precancerous lesions, we cannot rely on observed and predicted trends in gastric cancer mortality and strongly recommend tailored surveillance programs

Struggling with COVID-19 in Adult Inborn Errors of Immunity Patients: A Case Series of Combination Therapy and Multiple Lines of Therapy for Selected Patients

Background: The SARS-CoV-2 infection is now a part of the everyday lives of immunocompromised patients, but the choice of treatment and the time of viral clearance can often be complex, exposing patients to possible complications. The role of the available antiviral and monoclonal therapies is a matter of debate, as are their effectiveness and potential related adverse effects. To date, in the literature, the amount of data on the use of combination therapies and on the multiple lines of anti-SARS-CoV-2 therapy available to the general population and especially to inborn error of immunity (IEI) patients is small. Methods: Here, we report a case series of five adult IEI patients managed as inpatients at three Italian IEI referral centers (Rome, Treviso, and Cagliari) treated with combination therapy or multiple therapeutic lines for SARS-CoV-2 infection, such as monoclonal antibodies (mAbs), antivirals, convalescent plasma (CP), mAbs plus antiviral, and CP combined with antiviral. Results: This study may support the use of combination therapy against SARS-CoV-2 in complicated IEI patients with predominant antibody deficiency and impaired vaccine response

Subcutaneous immunoglobulins replacement therapy in secondary antibody deficiencies: real life evidence as compared to primary antibody deficiencies

Secondary antibody deficiencies (SAD) may require immunoglobulin replacement therapy (IgRT). While the intravenous route (IVIG) is broadly considered effective in SAD, the use of subcutaneous immunoglobulins (SCIG) is mainly adopted from the experience in primary antibody deficiencies (PAD), where SCIG have been shown to perform as effective as IVIG. However, evidence-based data on SCIG administration in SAD patients are still insufficient. Herein we retrospectively evaluated the efficacy and safety profile of SCIG treatment in 131 SAD patients as compared to a group of 102 PAD patients. We found SCIG being equally effective in reducing annual infectious rate both in SAD and PAD patients. However, SAD patients required lower SCIG dosage and lower IgG through level to achieve similar biological effect in terms of infection burden, at the steady state. SAD patients also showed better correlation between SCIG dose and serum IgG achieved value. Furthermore, within SAD, SCIG were found to work irrespective of the underlying disease. Especially in Non-Hodgkin Lymphoma patients, whose indication to IgRT is still not included in all guidelines and for whom evidence-based data are still lacking, SCIG were as effective as in Chronic Lymphocytic Leukemia or Multiple Myeloma patients, and SCIG discontinuation, without evidence of B cell recovery, led to IgG decline and relapsed infections. Finally, treatment tolerance in SAD patients was comparable to the PAD cohort. Globally, our data suggest that SCIG, as already appreciated in PAD, represent a valuable option in SAD patients, independent on the disease leading to antibody deficiency

Non cross-linked equine collagen (Salvecoll-E gel) for treatment of complex ano-rectal fistula

Summary: Background: Fistula-in-ano is one of the most commonly presenting anorectal diseases. Sphincter sparing treatment options should be considered in patients with complex fistulas. Salvecoll-E gel is a native collagen deantigenated and purified, non-cross-linked equine dermal extract, with an amino acid composition identical to human collagen. Methods: The multicentric trial study was a prospective, single-arm observational clinical study with the objective to assess the efficacy of Salvecoll-E gel for anal fistula repair in 70 patients. All patients had undergone preliminary surgical treatment consisting of positioning of a draining loosing seton that was maintained for a period of 4–6 weeks. After seton removal, a gentle debridement and washing of the fistula track was performed. The scar tissue was removed from the internal orifice. Internal opening was covered by a side-to side mucosal suture. Salvecoll-E was injected through the external opening into the fistula track, the external opening it has been opened. Results: Twelve months after surgery, 55 patients demonstrated a clinically healed fistula (78,5%), 15 patients have a recurrence (21,5%). Most of the recurrences were observed in the first 6 months of treatment (13/15, 86.6%). We don't observe any worsening in CCF score. The results obtained at 1 year certainly seem satisfactory and in line with the best results published in literature using mini-invasive techniques. Conclusion: Salvecoll-E gel is a promising non-invasive technique for conservative treatment of anal fistulas, it's well tolerated by the patients and, in case of recurrence, reinjection or all other known techniques are feasible. Keywords: Complex ano-rectal fistula, Non cutting technique, Mini-invasive treatmen