15 research outputs found
COVID-19, Pre-Eclampsia, and Complement System
No full textCopyright © 2021 Agostinis, Mangogna, Balduit, Aghamajidi, Ricci, Kishore and Bulla. COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.Ferring COVID-19 Investigational Grant (GRAVISAR to RB); Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy (RC24/19 to GR and 09/21 to CA)
The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer
No full textSIMPLE SUMMARY: The gut microbiome affects the development of systemic immune response and it can also impact response to systemic treatments such as immunotherapy and chemotherapy. This article provides and in-depth overview of various mechanisms that the gut microbiome interacts with the immune system, cancer, and how it affects anti-tumor immunity and response to immunotherapy. ABSTRACT: Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Microbiota-induced inflammation possibly contributes to tumor growth and cancer development. Microbiota-derived metabolites can also be converted to carcinogenic agents related to genetic mutations and DNA damage in organs such as the colon. However, other attributes of microbiota, such as greater diversity and specific bacterial species and their metabolites, are linked to better clinical outcomes and potentially improved anti-tumor immunity. In addition, the intratumoral microbial composition strongly affects T-cell-mediated cytotoxicity and anti-tumor immune surveillance, adding more complexity to the cancer-microbiome-immune axis. Despite the emerging clinical evidence for the activity of the gut microbiota in immuno-oncology, the fundamental mechanisms of such activity are not well understood. This review provides an overview of underlying mechanisms by which the gut microbiota and its metabolites enhance or suppress anti-tumor immune responses. Understanding such mechanisms allows for better design of microbiome-specific treatment strategies to improve the clinical outcome in cancer patients undergoing systemic therapy
The attentive focus on T cell‐mediated autoimmune pathogenesis of psoriasis, lichen planus and vitiligo
No full textPeripheral blood lymphocytes are able to maintain their viability and basic function in normal urine
No full textBackground: Similar to inflammatory cells, peripheral blood mononuclear cells (PBMCs) can also infiltrate in to kidney and urinary tracts and subsequently excreted by urine. In this study we determined the viability rate and response to phytohemagglutinin-A (PHA) of human PBMCs in normal urine.
Methods: A number of 1×106 ficoll-hypaque isolated PBMCs were dispensed in 1 ml normal urine and 6 molar urea and RPMI-1640+FBS10 % were considered as negative and positive control, respectively. After 20, 60 and 120 minutes the viability of these cells was measured by trypan blue dye exclusion assay. 1×105 of PBMCs were isolated from urine and cultured as triplicate in RPMI-1640`supplemented with FBS 10% and PHA for 96hr. MTT assay was performed to determine the PBMCs response to PHA. These experiments were repeated three times independently.
Results: There was no significant difference between the viability rates of the PBMCs incubated in urine and positive control after 20, 60 and 120 minutes while after 60 minutes they exhibited 75.6% of reactivity to PHA versus positive control. Overall, there was a significant difference in trends of viability rate across the three groups (p<0.05).
Conclusion: Our results showed that not only PBMCs remained alive in urine after 120 minutes, but can also respond to PHA up to 60 minutes at a remarkable level. These data open a new avenue in the designation for cell culture-based techniques in urine cell analysis
The roles of interleukin‐1 receptor accessory protein in certain inflammatory conditions
No full textInterleukin-1 receptor accessory protein (IL-1RAcP) is a member of the immunoglobulin superfamily proteins consisting of soluble and membranous isoforms. IL-1RAcP plays an essential role in the signaling of the IL-1 family cytokines such as IL-1, IL-33 and IL-36, as well as tyrosine kinases FLT3 and C-Kit. IL-1RAcP generally initiates inflammatory signaling pathway through the recruitment of signaling mediators, including MYD88 and IRAK. Chronic inflammation following prolonged signaling of cytokine receptors is a critical process in the pathogenesis of many inflammatory disorders, including autoimmunity, obesity, psoriasis, type 1 diabetes, endometriosis, preeclampsia and Alzheimer's disease. Recently IL-1RAcP aberrant signaling has been considered to play a central role in the pathogenesis of these chronic inflammatory diseases. Targeting IL-1RAcP signaling pathway that was recently considered in clinical trials related to malignancies also indicates its potential as therapeutic target for the inflammatory and autoimmune diseases. This review summarizes the molecular structure, components associated with IL-1RAcP signaling pathways, and their involvement in the pathogenesis of different inflammatory diseases. We will also discuss the effect of IL-1RAcP inhibition for treatment proposes
Patients with Coronary Artery Disease Have Lower Levels of Antibody to Heat-Stressed Fibroblast Derived Proteins, versus Normal Subjects
No full textCellular stress response plays an important role in the pathophysiology of coronary artery disease (CAD). Inhibition of cellular stress may provide a novel clinical approach regarding the diagnosis and treatment of CAD. Fibroblasts constitute 60-70% of cardiac cells and have a crucial role in cardiovascular function. Hence, the aim of this study was to show a potential therapeutic application of proteins derived from heat-stressed fibroblast in CAD patients. Fibroblasts were isolated from the foreskin and cultured under heat stress conditions. Surprisingly, 1.06% of the cells exhibited a necrotic death pattern. Furthermore, heat-stressed fibroblasts produced higher level of total proteins than control cells. In SDS-PAGE analysis, a 70 kDa protein band was observed in stressed cell culture supernatants which appeared as two acidic spots with close pI in the two-dimensional electrophoresis. To evaluate the immunogenic properties of fibroblast-derived heat shock proteins (HSPs), the serum immunoglobulin-G (IgG) was measured by ELISA in 50 CAD patients and 50 normal subjects who had been diagnosed through angiography. Interestingly, the level of anti-HSP antibody was significantly higher in non-CAD individuals in comparison with the patient’s group (p<0.05). The odds ratio for CAD was 5.06 (95%CI=2.15‐11.91) in cut-off value of 30 AU/mL of anti-HSP antibody. Moreover, ROC analysis showed that anti-HSP antibodies had a specificity of 74% and a sensitivity of 64%, which is almost equal to 66% sensitivity of exercise stress test (EST) as a CAD diagnostic method. These data revealed that fibroblast-derived HSPs are suitable for the diagnosis and management of CAD through antibody production
B lymphocytes in COVID-19: a tale of harmony and discordance
No full textB lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection
Comprehensive Analysis of Global Research on Human Varicocele: A Scientometric Approach
No full textPurpose: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair. Materials and Methods: Varicocele studies published between 1988 and 2020 were retrieved from the Scopus database on April 5, 2021. Original studies on human varicocele were included, irrespective of language. Retrieved articles were manually screened for inclusion in various sub-categories. Bibliometric data was subjected to scientometric analysis using descriptive statistics. Network, heat and geographic mapping were generated using relevant software. Results: In total, 1,943 original human studies on varicocele were published. These were predominantly from the northern hemisphere and developed countries, and published in journals from the United States and Germany. Network map analysis for countries showed several interconnected nodal points, with the USA being the largest, and Agarwal A. from Cleveland Clinic, USA, being a center point of worldwide varicocele research collaborations. Studies of adolescents were underrepresented compared with studies of adults. Studies on diagnostic and prognostic aspects of varicocele were more numerous than studies on varicocele prevalence, mechanistic studies and studies focusing on etiological and risk factors. Varicocele surgery was more investigated than non-surgical approaches. To evaluate the impact of varicocele and its treatment, researchers mainly analyzed basic semen parameters, although markers of seminal oxidative stress are being increasingly investigated in the last decade, while reproductive outcomes such as live birth rate were under-reported in the literature. Conclusions: This study analyzes the publication trends in original research on human varicocele spanning over the last three decades. Our analysis emphasizes areas for further exploration to better understand varicocele's impact on men's health and male fertility
Comprehensive Analysis of Global Research on Human Varicocele: A Scientometric Approach
No full textPurpose: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair. Materials and Methods: Varicocele studies published between 1988 and 2020 were retrieved from the Scopus database on April 5, 2021. Original studies on human varicocele were included, irrespective of language. Retrieved articles were manually screened for inclusion in various sub-categories. Bibliometric data was subjected to scientometric analysis using descriptive statistics. Network, heat and geographic mapping were generated using relevant software. Results: In total, 1,943 original human studies on varicocele were published. These were predominantly from the northern hemisphere and developed countries, and published in journals from the United States and Germany. Network map analysis for countries showed several interconnected nodal points, with the USA being the largest, and Agarwal A. from Cleveland Clinic, USA, being a center point of worldwide varicocele research collaborations. Studies of adolescents were underrepresented compared with studies of adults. Studies on diagnostic and prognostic aspects of varicocele were more numerous than studies on varicocele prevalence, mechanistic studies and studies focusing on etiological and risk factors. Varicocele surgery was more investigated than non-surgical approaches. To evaluate the impact of varicocele and its treatment, researchers mainly analyzed basic semen parameters, although markers of seminal oxidative stress are being increasingly investigated in the last decade, while reproductive outcomes such as live birth rate were under-reported in the literature. Conclusions: This study analyzes the publication trends in original research on human varicocele spanning over the last three decades. Our analysis emphasizes areas for further exploration to better understand varicocele's impact on men's health and male fertility.Peer reviewe
THE IMPACT OF VARICOCELE REPAIR ON CONVENTIONAL SEMEN PARAMETERS IN INFERTILE MEN: A META-ANALYSIS USING PRE- AND POST-OPERATIVE DATA
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