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Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice.
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Background: Cardiovascular (CV) disease is the leading cause of death in women, but few of them are aware of the CV risks (CVRs). Most women are not aware of all the CV risk factorsand their knowledge often still does not improve their lifestyle. Methods: The Carin Women is a survey conducted among Italian women by filling out a questionnaire in the waiting rooms of clinics. The aim was to determine the level of awareness of women's cardiovascular risk, knowledge of risk factors, and lifestyle. A total of 5590 questionnaires were completed in two different periods. Results: Median age was 56 (IQR 46-65); BMI was 25 (IQR 22-29). Schooling, marital status, and rate of risk conditions were assessed; 311 women (5.57%) had already suffered a cardiovascular event. The relationship between the CV events and the number of traditional risk factors was significant. A similar curve, but without significant differences, was reported for non-traditional risk factors. From the total number of women, 23% with a high CVR and 62% with a very high CVR underestimated thei risk regardless of their level of education. Up to 43% of women underestimated female CV risk compared to male risk. Women showed a good knowledge of traditional risk factors, but only a few of them had a healthy lifestyle: 21.86% were smokers, only 45.88% performed sufficient physical activity, 27.55% did not recognize they were overweight, and only 30.4% consumed more than two daily portions of fruit and vegetables. Most women (86%) need more information about CVR. Conclusions: Italian women underestimate female CVRs and their own CVR.
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Proteolytic release of transmembrane proteins from the cell surface, the so called ectodomain shedding, is a key process in inflammation. Inactive rhomboid 2 (iRhom2) plays a crucial role in this context, in that it guides maturation and function of the sheddase ADAM17 (a disintegrin and metalloproteinase 17) in immune cells, and, ultimately, its ability to release inflammatory mediators such as tumor necrosis factor α (TNFα). Yet, the macrophage sheddome of iRhom2/ADAM17, which is the collection of substrates that are released by the proteolytic complex, is only partly known. In this study, we applied high-resolution proteomics to murine and human iRhom2-deficient macrophages for a systematic identification of substrates, and therefore functions, of the iRhom2/ADAM17 proteolytic complex. We found that iRhom2 loss suppressed the release of a group of transmembrane proteins, including known (e.g. CSF1R) and putative novel ADAM17 substrates. In the latter group, shedding of major histocompatibility complex class I molecules (MHC-I) was consistently reduced in both murine and human macrophages when iRhom2 was ablated. Intriguingly, it emerged that in addition to its shedding, iRhom2 could also control surface expression of MHC-I by an undefined mechanism. We have demonstrated the biological significance of this process by using an in vitro model of CD8+ T-cell (CTL) activation. In this model, iRhom2 loss and consequent reduction of MHC-I expression on the cell surface of an Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line dampened activation of autologous CTLs and their cell-mediated cytotoxicity. Taken together, this study uncovers a new role for iRhom2 in controlling cell surface levels of MHC-I by a dual mechanism that involves regulation of their surface expression and ectodomain shedding.
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Proteínas Portadoras , Infecciones por Virus de Epstein-Barr , Animales , Humanos , Ratones , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Proteínas Portadoras/metabolismo , Herpesvirus Humano 4 , Complejo Mayor de Histocompatibilidad , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones NoqueadosRESUMEN
Background: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. ARCA-post-COVID is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one. We performed anamnesis, lab-test, and routine cardiological tests (ECG, Holter, TTE). Results: The median age was 56 years (IQR 44-67); women were 52.19%; in the acute phase 24.1% of patients were treated in a medical department, 7.2% in the ICU and the others at home. At the visit, 389 patients (77.49%) complained of a broad range of symptoms. We reported patients' characteristics according to the course of the disease and the persistence of symptoms. NCA were found in 138 patients (27.49%): among them 60 cases (11.95%) of pericardial effusion. Patients with NCA were older (median 60y, IQR: 47-72, vs median 56y, IQR 42-65), had a higher prevalence of smokers (27% vs 17%; p0.014), CAD (11% vs 6%; p0.048) and stroke/TIA (3.6% vs 0.3%; p0.002) and a lower prevalence of hypercholesterolemia (18% vs 30%; p0.007). The prevalence of NCA seems constant with different subtypes of the virus. Conclusion: the prevalence of NCA in patients who recovered from COVID-19 is high and constant since the beginning of the pandemic; it is predictable based on hospitalization and long-lasting symptoms (9.64%-42.52%). Patients with one of these characteristics should undergo cardiological screening.
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Pancreatic cancer (PCa) is the fifth leading cause of cancer mortality. Recently, our group and others have demonstrated the oncolytic activity of the Zika virus (ZIKV) against glioblastoma. The peculiar features of this virus offer the opportunity to use an agent already tested in vivo through natural transmission, with minimal effects on adults, to specifically target a tumor such as glioblastoma. This remarkable specificity prompted us to explore the potential use of ZIKV oncolytic action against other tumor types. In particular, we focused on the subgroup of pancreatic tumors with a neuroendocrine origin known as neuroendocrine tumors (NETs). We found that ZIKV exerts its oncolytic activity by specifically infecting NET cells, leading to growth inhibition and cell death. We also assessed whether the oncolytic action could be extended to pancreatic tumors different from NETs. However, as expected, the viral specificity is limited to NETs and is not applicable to adenocarcinoma tumors, indicating a narrow spectrum of action for this virus. These findings support the potential use of ZIKV in therapeutic approaches not only in glioblastoma, but also against other tumors, such as neuroendocrine pancreatic tumors.
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Glioblastoma , Tumores Neuroendocrinos , Viroterapia Oncolítica , Virus Oncolíticos , Neoplasias Pancreáticas , Infección por el Virus Zika , Virus Zika , Adulto , Humanos , Virus Zika/fisiología , Glioblastoma/terapia , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Hormonas PancreáticasRESUMEN
Neural stem cells (NSCs) were described for the first time more than two decades ago for their ability to differentiate into all neural cell lineages. The isolation of NSCs from adults and embryos was carried out by various laboratories and in different species, from mice to humans. Similarly, no more than two decades ago, cancer stem cells were described. Cancer stem cells, previously identified in hematological malignancies, have now been isolated from several solid tumors (breast, brain, and gastrointestinal compartment). Though the origin of these cells is still unknown, there is a wide consensus about their role in tumor onset, propagation and, in particular, resistance to treatments. Normal and neoplastic neural stem cells share common characteristics, and can thus be considered as two sides of the same coin. This is particularly true in the case of the Zika virus (ZIKV), which has been described as an inhibitor of neural development by specifically targeting NSCs. This understanding prompted us and other groups to evaluate ZIKV action in glioblastoma stem cells (GSCs). The results indicate an oncolytic activity of this virus vs. GSCs, opening potentially new possibilities in glioblastoma treatment.
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Glioblastoma , Infección por el Virus Zika , Virus Zika , Adulto , Humanos , Animales , Ratones , Glioblastoma/terapia , Células Madre Neoplásicas , EncéfaloRESUMEN
Mesenchymal stromal/stem cells (MSCs) have emerged as a therapeutic tool in regenerative medicine. Recent studies have shown that exosome (EXO)-derived microRNAs (miRNAs) play a crucial role in mediating MSC functions. Additionally, intracellular miRNAs have been found to regulate MSC therapeutic capacities. However, the molecular mechanisms underlying miRNA-mediated MSC effects are not fully understood. We used 3D culture and IFN-γ to prime/enhance the MSC therapeutic effects in terms of functional miRNAs. After priming, our analysis revealed stable variations in intracellular miRNA among the MSC biological replicates. Conversely, a significant variability of miRNA was observed among EXOs released from biological replicates of the priming treatment. For each priming, we observed distinct miRNA expression profiles between the MSCs and their EXOs. Moreover, in both types of priming, gene ontology (GO) analysis of deregulated miRNAs highlighted their involvement in tissue repair/regeneration pathways. In particular, the 3D culture enhanced angiogenic properties in both MSCs and EXOs, while IFN-γ treatment enriched miRNAs associated with immunomodulatory pathways. These findings suggest that 3D culture and IFN-γ treatment are promising strategies for enhancing the therapeutic potential of MSCs by modulating miRNA expression. Additionally, the identified miRNAs may contribute to understanding the molecular mechanisms underlying the miRNA-mediated therapeutic effects of MSCs.
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BACKGROUND: Ischemia/reperfusion injury (IRI), acute rejection (AR), and delayed graft function (DGF) might occur as major complications following kidney transplantation. Thus, the identification of biomarkers for the IRI, AR, and/or DGF development becomes crucial as it may help to guide post-transplant management. Natural killer (NK) cells, hepatic interstitial T-lymphocytes (T-Li), and NK-T cells are crucial in both innate and adaptive immunity after abdominal solid organ transplantation. Hence, the aim of this study was to evaluate the impact of the immune system after graft reperfusion during KT in adults in order to identify predictive biomarkers. METHODS: The NK, T-Li, and NK-T phenotypes and concentrations were retrospectively analyzed in a consecutive series of liver perfusates obtained after organ procurement flushing the abdominal cavity recovered from deceased brain donors (DBDs). Their percentage was compared with the renal transplant recipients' characteristics with kidneys taken from the same DCDs. The hepatic perfusate cells were purified by density gradient centrifugation. Flow cytometric investigation was used to determine their phenotype with the following immunological markers in order to determine the relative percentage of T-Li, NK-T, and NK cells: CD3, CD4, CD8, and CD56. RESULTS: 42 DBDs' liver perfusates were analyzed. The related clinical outcomes of kidney transplant recipients from 2010 to 2020 performed at our Institute were evaluated. Time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02) and the onset of secondary infection from a cytomegalovirus (p = 0.03) were significantly associated with the T-Li percentage. An increased relative risk (HR) of organ survival was significantly associated with the percent cell concentration of T-Li and time to DGF, on COX analysis, were (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). None relevant clinical outcomes in kidney transplant patients were associated with the specificity of the NK and NK-T cell proportions. CONCLUSIONS: A new potential role of T-Li cells was detected in the context of hepatic perfusate from DBDs. It could detect potential impacts in organ allocation, surgical procuring techniques, and in the analysis of IRI pathophysiological events.
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Mesenchymal stromal/stem cells (MSCs) have shown significant therapeutic potential, and have therefore been extensively investigated in preclinical studies of regenerative medicine. However, while MSCs have been shown to be safe as a cellular treatment, they have usually been therapeutically ineffective in human diseases. In fact, in many clinical trials it has been shown that MSCs have moderate or poor efficacy. This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs. Recently, specific priming strategies have been used to improve the therapeutic properties of MSCs. In this review, we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs. We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes. Particularly, while hypoxic priming can be used primarily for the treatment of acute diseases, inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders. The shift in approach from regeneration to inflammation implies, in MSCs, a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways. The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.
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Ischemia/reperfusion injury (IRI) is a multistep damage that occurs in several tissues when a blood flow interruption is inevitable, such as during organ surgery or transplantation. It is responsible for cell death and tissue dysfunction, thus leading, in the case of transplantation, to organ rejection. IRI takes place during reperfusion, i.e., when blood flow is restored, by activating inflammation and reactive oxygen species (ROS) production, causing mitochondrial damage and apoptosis of parenchymal cells. Unfortunately, none of the therapies currently in use are definitive, prompting the need for new therapeutic approaches. Scientific evidence has proven that mesenchymal stem/stromal cells (MSCs) can reduce inflammation and ROS, prompting this cellular therapy to also be investigated for treatment of IRI. Moreover, it has been shown that MSC therapeutic effects were mediated in part by their secretome, which appears to be involved in immune regulation and tissue repair. For these reasons, mediated MSC paracrine function might be key for injury amelioration upon IRI damage. In this review, we highlight the scientific literature on the potential beneficial use of MSCs and their products for improving IRI outcomes in different tissues/organs, focusing in particular on the paracrine effects mediated by MSCs, and on the molecular mechanisms behind these effects.
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BACKGROUND: Type 2 diabetes mellitus is associated with a cluster of lipid and apolipoprotein abnormalities which increase the risk for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the adherence to guidelines-oriented dyslipidemia treatment in diabetic patients and to assess the efficacy of a territorial goal-oriented program. METHODS: One thousand seventy-one diabetic patients at very high cardiovascular risk were enrolled in this prospective study. They performed a clinical-laboratory follow-up program, received lifestyle recommendations and optimization of their antihyperlipidemic therapies. At the beginning and the 3-month follow-up visit, LDL-c data were collected, and further therapies were prescribed to the patients that did not reach the target. After 12 month follow-up, LDL-c data were collected again. RESULTS: Diabetic patients significantly improved mean LDL cholesterol levels during one-year follow-up (LDLc mean value 135 mg/dL at baseline, 60 mg/dL at the end of the study), obtaining a greater reduction compared to non-diabetic patients participating in the same program. Accordingly, the percentage of patients that reached the lipid target was significantly higher in diabetic patients after 3-months and 12- follow-ups (P<0.05). Diabetic patients assuming statins, both in monotherapy and in combination with ezetimibe, increased during the follow-up (74.1% at the enrolment vs. 88.2% one year later). GLP1ra-treated patients achieved the greatest reduction in cholesterol levels compared to baseline. CONCLUSIONS: The results of the study recommend encouraging strategies and appropriate treatments to achieve a targeted lipid profile in diabetic patients at very high cardiovascular risk.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Humanos , Objetivos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , LDL-Colesterol , Estudios Prospectivos , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiologíaRESUMEN
At present, there is a lack of clinical evidence about the impact and long-term durability of the immune response induced by the third dose of mRNA vaccines. In this study, we followed up the B cell compartment behavior in a cohort of immunocompetent individuals three and six months after the third dose of vaccine. During this period, some subjects contracted the virus. In uninfected vaccinated subjects, we did not report any changes in serum spike-specific IgG levels, with a significant reduction in IgA. Instead, subjects recovered from natural infection showed a significant increase in both specific IgG and IgA. Moreover, we showed a time-related decrease in IgG neutralizing potential to all SARS-CoV-2 variants of concern (VOC) in uninfected compared to recovered subjects, who displayed an increased neutralizing ability, particularly against the omicron variant. Finally, we underlined the presence of a pool of SARS-CoV-2-specific B cells in both groups that are prone to respond to restimulation, as demonstrated by their ability to differentiate into plasma cells and to produce anti-SARS-CoV-2-specific immunoglobulins. These data lead us to assert the long-term effectiveness of the BNT162b2 vaccine in contrasting the severe form of the pathology and prevent COVID-19-associated hospitalization.
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COVID-19 , Células B de Memoria , Humanos , SARS-CoV-2 , Vacuna BNT162 , COVID-19/prevención & control , ARN Mensajero/genética , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
The coronavirus-19 disease (COVID-19) related pandemic have deeply impacted human health, economy, psychology and sociality. Possible serious cardiac involvement in the infection has been described, raising doubts about complete healing after the disease in many clinical settings. Moreover, there is the suspicion that the vaccines, especially those based on mRNA technology, can induce myopericarditis. Myocarditis or pericarditis related scars can represent the substrate for lifethreatening arrhythmias, triggered by physical activity. A crucial point is how to evaluate an athlete after a Covid-19 infection ensuring a safe return to play without increasing the number of unnecessary disqualifications from sports competitions. The lack of conclusive scientific data significantly increases the difficulty to propose recommendations and guidelines on this topic. At the same time, the psychological and physical negative consequences of unnecessary sports restriction must be taken into account. The present document aims to provide an updated brief review of the current knowledge about the COVID-19 cardiac involvement and how to recognize it and to offer a roadmap for the management of the athletes after a Covid-19 infections, including subsequent impact on exercise recommendations. Our document exclusively refers to cardiovascular implications of the disease, but pulmonary consequences are also considered.
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Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%-20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , MicroARNs , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/genética , Hepatitis C/patología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , MicroARNs/genética , MicroARNs/uso terapéuticoRESUMEN
Current international guidelines strongly recommend the use of high-intensity lipid-lowering therapy (LLT) after hospitalization for atherosclerotic cardiovascular disease (ASCVD) events. With this study, our aim was to evaluate LLT prescribing in a large Italian cohort of patients after discharge for an ASCVD event, exploring factors associated with a lower likelihood of receiving any LLT and high-intensity LLT. Individuals aged 18 years and older discharged for an ASCVD event in 2019-2020 were identified using hospital discharge abstracts from two local health units of the Campania region. LLT treatment patterns were analyzed in the 6 months after the index event. Logistic regression models were developed for estimating patient predictors of any LLT prescription and to compare high-intensity and low-to-moderate-intensity LLT. Results: A total of 8705 subjects were identified. In the 6 months post-discharge, 56.7% of patients were prescribed LLT and, of those, 48.7% were high-intensity LLT. Female sex, older age, and stroke/TIA or PAD conditions were associated with a higher likelihood of not receiving high-intensity LLT. Similar predictors were found for LLT prescriptions. LLT utilization and the specific use of high-intensity LLT remain low in patients with ASCVD, suggesting a substantial unmet need among these patients in the contemporary real-world setting.
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Chondrosarcoma is the second most common bone tumor, accounting for 20% of all cases. Little is known about the pathology and molecular mechanisms involved in the development and in the metastatic process of chondrosarcoma. As a consequence, there are no approved therapies for this tumor and surgical resection is the only treatment currently available. Moreover, there are no available biomarkers for this type of tumor, and chondrosarcoma classification relies on operator-dependent histopathological assessment. Reliable biomarkers of chondrosarcoma are urgently needed, as well as greater understanding of the molecular mechanisms of its development for translational purposes. Hypoxia is a central feature of chondrosarcoma progression. The hypoxic tumor microenvironment of chondrosarcoma triggers a number of cellular events, culminating in increased invasiveness and migratory capability. Herein, we analyzed the effects of chemically-induced hypoxia on the secretome of SW 1353, a human chondrosarcoma cell line, using high-resolution quantitative proteomics. We found that hypoxia induced unconventional protein secretion and the release of proteins associated to exosomes. Among these proteins, which may be used to monitor chondrosarcoma development, we validated the increased secretion in response to hypoxia of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme well-known for its different functional roles in a wide range of tumors. In conclusion, by analyzing the changes induced by hypoxia in the secretome of chondrosarcoma cells, we identified molecular mechanisms that can play a role in chondrosarcoma progression and pinpointed proteins, including GAPDH, that may be developed as potential biomarkers for the diagnosis and therapeutic management of chondrosarcoma.
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BACKGROUND: The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. METHODS: SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d posttransplant; secondary end-points were severe complications. RESULTS: The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% ( P = 0.016) and 89.66% ( P = 0.080) at 90 d and 86.21% ( P = 0.041) and 86.2% ( P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group ( P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d ( P = 0.017), ( P = 0.015) in the simvastatin group. CONCLUSIONS: Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Trasplante de Hígado , Adulto , Humanos , Trasplante de Hígado/efectos adversos , Simvastatina/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Estudios Prospectivos , Donantes de Tejidos , Supervivencia de Injerto , Resultado del TratamientoRESUMEN
Cancer immunotherapy has led to impressive advances in cancer treatment. Unfortunately, in a high percentage of patients is difficult to consistently restore immune responses to eradicate established tumors. It is well accepted that adaptive immune cells, such as B lymphocytes, CD4+ helper T lymphocytes, and CD8+ cytotoxic T-lymphocytes (CTLs), are the most effective cells able to eliminate tumors. However, it has been recently reported that innate immune cells, including natural killer cells (NK), dendritic cells (DC), macrophages, myeloid-derived suppressor cells (MDSCs), and innate lymphoid cells (ILCs), represent important contributors to modulating the tumor microenvironment and shaping the adaptive tumor response. In fact, their role as a bridge to adaptive immunity, make them an attractive therapeutic target for cancer treatment. Here, we provide a comprehensive overview of the pleiotropic role of tissue-resident innate immune cells in different tumor contexts. In addition, we discuss how current and future therapeutic approaches targeting innate immune cells sustain the adaptive immune system in order to improve the efficacy of current tumor immunotherapies.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is modifying human activity all over the world with significant health and economic burden. The advent of the SARS-CoV-2 pandemic prompted the scientific community to learn the virus dynamics concerning transmissibility, epidemiology, and usefulness of vaccines in fighting emerging health hazards. Pieces of evidence suggest that the first and second doses of mRNA vaccines induce a significant antibody response in vaccinated subjects or patients who recovered from SARS-CoV-2 infection, demonstrating the importance of the previously formed memory. The aim of this work has been to investigate the effects of BNT162b2 Pfizer-BioNTech mRNA-based vaccine booster dose in a cohort of 11 uninfected immunocompetent (ICs), evaluating the humoral and cellular responses, with more carefulness on memory B and T cells. Our findings underscore the potential benefit of the third dose of mRNA vaccine on the lifespan of memory B and T cells, suggesting that booster doses could increase protection against SARS-CoV-2 infection.
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COVID-19 , SARS-CoV-2 , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunidad Celular , ARN Mensajero/genética , Linfocitos T , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
Principles and processes of comprehensive geriatric assessment (CGA) are increasingly being applied to subspecialties and subspecialty conditions, including cardiovascular patients (i.e., infective endocarditis; considerations of surgery or transcatheter aortic valve replacement, TAVR, for patients with aortic stenosis; vascular surgery) and postoperative mortality risk. In cardiovascular field CGA has mainly the aim to define ideal management according to the different typology of older adult patients (e.g., robust versus intermediate versus physical and cognitively disabled versus end-stage or dying), allowing physicians to select different therapeutic goals according to life expectancy; Aspect to be valued are by CGA are global health status and patient's decision-making capacity: CGA allows the individualized treatment definition and optimize the preprocedure condition.