Search Results (13)

Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores the importance of immune dysregulation. Morphea, an inflammatory skin disorder, may signal hematological involvement, as seen in deep morphea and post-radiotherapy lesions. Syndromic albinism, linked to various genetic mutations affecting melanin production, often presents with hematologic abnormalities. Treatment approaches focus on targeting the immune pathways specific to the condition, and when that is not possible, managing symptoms. Understanding these dermatological manifestations is crucial for the timely diagnosis and management of hematological disorders. Full article

Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell–cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer. Full article

Oxidative stress represents a hallmark for many degenerative pathologies of the Central Nervous System. Throughout life, the constant pressure of noxious stimuli and/or episodes of traumatic events may expose the brain to a microenvironment where the non-balanced reactive oxygen species inevitably lead to neuronal loss and cognitive decline. HO-1, a 32 kDa heat-shock protein catalyzing the degradation of heme into carbon monoxide (CO), iron and biliverdin/bilirubin is considered one of the main antioxidant defense mechanisms playing pivotal roles in neuroprotection. Restoring the redox homeostasis is the goal of many natural or synthetic antioxidant molecules pursuing beneficial effects on brain functions. Here, we investigated the antioxidant capacity of four selected benzofuran-2-one derivatives in a cellular model of neurodegeneration represented by differentiated SH-SY5Y cells exposed to catechol-induced oxidative stress. Our main results highlight how all the molecules have antioxidant properties, especially compound 9, showing great abilities in reducing intracellular ROS levels and protecting differentiated SH-SY5Y cells from catechol-induced death. This compound above all seems to boost HO-1 mRNA and perinuclear HO-1 protein isoform expression when cells are exposed to the oxidative insult. Our findings open the way to consider benzofuran-2-ones as a novel and promising adjuvant antioxidant strategy for many neurodegenerative disorders. Full article

The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL. Full article

HLA class II molecules are key factors determining susceptibility to autoimmune disorders, and their role in immune-mediated skin conditions such as psoriasis has been extensively investigated. However, there is currently little understanding of their role in antibody-mediated skin diseases such as autoimmune blistering disorders. We researched the available literature using PubMed to narratively review the current knowledge on HLA associations in antibody-mediated blistering skin pathologies. Our results summarized the risk alleles that are identified in the literature, together with certain known protective alleles: in the pemphigus group, alleles HLA-DQB1*0503 and HLA-DRB1*0402 are most commonly associated with disease; in the pemphigoid group, the most studied allele is HLA-DQB1*0301; in epidermolysis bullosa acquisita, few genetic studies are available; in dermatitis herpetiformis, the association with haplotypes HLA-DQ2 and HLA-DQ8 is strongly established; finally, in linear IgA bullous disease, specific HLA alleles may be responsible for pediatric presentations. Our current pathogenic understanding of this group of disorders assigns a key role to predisposing HLA class II alleles that are able to bind disease autoantigens and therefore stimulate antigen-specific autoreactive T cells. The latter engage B lymphocytes that will produce pathogenic autoantibodies. The distribution of HLA alleles and their disease associations are variable across demographics, and an in-depth pathogenetic understanding is needed to support associations between HLA alleles and disease phenotypes. Additionally, in a personalized medicine approach, the identification of HLA alleles associated with the risk of disease may become clinically relevant in identifying susceptible subjects that should avoid exposure to known triggers, such as medication, when possible. Full article

The introduction of monoclonal antibodies such as rituximab to the treatment of cancer has greatly advanced the treatment scenario in onco-hematology. However, the response to these agents may be limited by insufficient efficacy or resistance. Antibody–drug conjugates are an attractive strategy to deliver payloads of toxicity or radiation with high selectivity toward malignant targets and limited unwanted effects. Primary cutaneous lymphomas are a heterogeneous group of disorders and a current area of unmet need in dermato-oncology due to the limited options available for advanced cases. This review briefly summarizes our current understanding of T and B cell lymphomagenesis, with a focus on recognized molecular alterations that may provide investigative therapeutic targets. The authors reviewed antibody-directed therapies investigated in the setting of lymphoma: this term includes a broad spectrum of approaches, from antibody–drug conjugates such as brentuximab vedotin, to bi-specific antibodies, antibody combinations, antibody-conjugated nanotherapeutics, radioimmunotherapy and, finally, photoimmunotherapy with specific antibody–photoadsorber conjugates, as an attractive strategy in development for the future management of cutaneous lymphoma. Full article

Recently, our research team has started a study on Brassica fruticulosa subsp. fruticulosa, an edible plant traditionally used to treat various ailments, little investigated to date. Good in vitro antioxidant properties were highlighted for the leaf hydroalcoholic extract, with the secondary higher than the primary ones. In continuation of the ongoing research, this work was designed to elucidate the antioxidant properties of the phenolic compounds contained in the extract. For this purpose, a phenolic-rich ethyl acetate fraction (Bff-EAF) was obtained from the crude extract by liquid–liquid extraction. The phenolic composition was characterized by HPLC-PDA/ESI-MS analysis and the antioxidant potential was investigated by different in vitro methods. Furthermore, the cytotoxic properties were evaluated by MTT, LDH and ROS determinations on human colorectal epithelial adenocarcinoma cells (CaCo-2) and human normal fibroblasts (HFF-1). Twenty phenolic compounds (flavonoid and phenolic acid derivatives) were identified in Bff-EAF. The fraction exhibited good radical scavenging activity in the DPPH test (IC₅₀ = 0.81 ± 0.02 mg/mL), and moderate reducing power (ASE/mL = 13.10 ± 0.94) and chelating properties (IC₅₀ = 2.27 ± 0.18 mg/mL), contrary to what previously observed for the crude extract. Bff-EAF reduced in a dose-dependent manner CaCo-2 cell proliferation after 72 h of treatment. This effect was accompanied by the destabilization of the cellular redox state due to the antioxidant and pro-oxidant activities displayed by the fraction at lower and higher concentrations. No cytotoxic effect was observed on HFF-1 fibroblasts, used as control cell line. Full article

Background: Cardiology divisions reshaped their activities during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to analyze the organization of echocardiographic laboratories and echocardiography practice during the second wave of the COVID-19 pandemic in Italy, and the expectations for the post-COVID era. Methods: We analyzed two different time periods: the month of November during the second wave of the COVID-19 pandemic (2020) and the identical month during 2019 (November 2019). Results: During the second wave of the COVID-19 pandemic, the hospital activity was partially reduced in 42 (60%) and wholly interrupted in 3 (4%) echocardiographic laboratories, whereas outpatient echocardiographic activity was partially reduced in 41 (59%) and completely interrupted in 7 (10%) laboratories. We observed an important change in the organization of activities in the echocardiography laboratory which reduced the operator-risk and improved self-protection of operators by using appropriate personal protection equipment. Operators wore FFP2 in 58 centers (83%) during trans-thoracic echocardiography (TTE), in 65 centers (93%) during transesophageal echocardiography (TEE) and 63 centers (90%) during stress echocardiography. The second wave caused a significant reduction in number of echocardiographic exams, compared to November 2019 (from 513 ± 539 to 341 ± 299 exams per center, −34%, p < 0.001). On average, there was a significant increase in the outpatient waiting list for elective echocardiographic exams (from 32.0 ± 28.1 to 45.5 ± 44.9 days, +41%, p < 0.001), with a reduction of in-hospital waiting list (2.9 ± 2.4 to 2.4 ± 2.0 days, −17%, p < 0.001). We observed a large diffusion of point-of-care cardiac ultrasound (88%), with a significant increase of lung ultrasound usage in 30 centers (43%) during 2019, extended to all centers in 2020. Carbon dioxide production by examination is an indicator of the environmental impact of technology (100-fold less with echocardiography compared to other cardiac imaging techniques). It was ignored in 2019 by 100% of centers, and currently it is considered potentially crucial for decision-making in cardiac imaging by 65 centers (93%). Conclusions: In one year, major changes occurred in echocardiography practice and culture. The examination structure changed with extensive usage of point-of-care cardiac ultrasound and with lung ultrasound embedded by default in the TTE examination, as well as the COVID-19 testing. Full article

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the “ABCDE protocol” of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study. Full article

A novel bioluminescent Monoacylglycerol lipase (MAGL) substrate 6-O-arachidonoylluciferin, a D-luciferin derivative, was synthesized, physico-chemically characterized, and used as highly sensitive substrate for MAGL in an assay developed for this purpose. We present here a new method based on the enzymatic cleavage of arachidonic acid with luciferin release using human Monoacylglycerol lipase (hMAGL) followed by its reaction with a chimeric luciferase, PLG2, to produce bioluminescence. Enzymatic cleavage of the new substrate by MAGL was demonstrated, and kinetic constants Km and Vmax were determined. 6-O-arachidonoylluciferin has proved to be a highly sensitive substrate for MAGL. The bioluminescence assay (LOD 90 pM, LOQ 300 pM) is much more sensitive and should suffer fewer biological interferences in cells lysate applications than typical fluorometric methods. The assay was validated for the identification and characterization of MAGL modulators using the well-known MAGL inhibitor JZL184. The use of PLG2 displaying distinct bioluminescence color and kinetics may offer a highly desirable opportunity to extend the range of applications to cell-based assays. Full article

Pesticide by-products found in soil are usually more toxic and persistent than the pesticides themselves. For example, Endosulfan lactone (EL) (a by-product of the organochloride pesticide endosulfan). EL is created by the enzymatic activity (and related oxidative processes) of microorganisms in the soil. A sustainable method of EL removal is the introduction of Eisenia fetida earthworm. In this paper, it will be demonstrated the impact of vermicomposting process related to Eisenia fetida earthworm on EL by measuring initial and final concentrations of the compound and overall enzymatic activity in sterile and non-sterile solid substrate over 56 days. As a baseline, it be observed there were higher EL removals in non-sterile solid substrate (90.86%) at day 5 than in sterile solid substrate (83.86%) at day 14. In samples with Eisenia fetida, the presence of EL in non-sterile solid substrate was 36%, however in sterile solid substrate it was only 18% at day 1 and 7, with a maximum enzyme activity of 0.4659 mmol/mg protein per min at day 7. The evidence found in this study suggests that EL removal in a non-sterile solid substrate is higher when a vermicomposting is present and that the influence of microorganisms from the solid substrate with the earthworm, increases removal. Full article

Endosulfan lactone is a metabolite obtained from the biological oxidation of the insecticide endosulfan by action of the microorganisms present in the soil. This metabolite is more toxic and persistent than the parent compound. Therefore, it is extremely important to be able to determine the presence of this metabolite in the soil. However, accessible methods for extraction of endosulfan lactone in soil were not found in published literature. For this reason, the aim of this study was to evaluate two conventional methods of liquid–solid extraction for the determination of endosulfan lactone in solid substrate using two solvents (ethyl acetate and acetonitrile) and HPLC UV-VIS. The acetonitrile and rotary agitation extraction method was the one with the highest efficiency (97%), optimized using a factorial 3² response surface design, and validated in terms of linearity and precision. The linearity shown was r > 0.999 in a wide spike level (0.15–100 mg kg⁻¹), with the detection limit (DL) of 0.045 mg kg⁻¹ and quantification limit (QL) of 0.15 mg kg⁻¹. The extraction of endosulfan lactone in solid substrate using acetonitrile was more efficient than that used with ethyl acetate, so this method could be used to extract and quantify endosulfan lactone in agricultural soil. Full article

Glutathione peroxidases (GPxs) form a broad family of antioxidant proteins essential for maintaining redox homeostasis in eukaryotic cells. In this study, we used an integrative approach that combines bioinformatics, molecular biology, and biochemistry to investigate the role of GPxs in reactive oxygen species detoxification in the unicellular eukaryotic model organism Tetrahymena thermophila. Both phylogenetic and mechanistic empirical model analyses provided indications about the evolutionary relationships among the GPXs of Tetrahymena and the orthologous enzymes of phylogenetically related species. In-silico gene characterization and text mining were used to predict the functional relationships between GPxs and other physiologically-relevant processes. The GPx genes contain conserved transcriptional regulatory elements in the promoter region, which suggest that transcription is under tight control of specialized signaling pathways. The bioinformatic findings were next experimentally validated by studying the time course of gene transcription and enzymatic activity after copper (Cu) exposure. Results emphasize the role of GPxs in the detoxification pathways that, by complex regulation of GPx gene expression, enable Tethraymena to survive in high Cu concentrations and the associated redox environment. Full article