Search Results (23)

Pressurized intra-thoracic aerosol chemotherapy (PITAC) is a novel and promising strategy for the treatment of malignant pleural effusion (MPE). PITAC enables effective pleurodesis while potentially exerting an antineoplastic effect by delivering chemotherapeutic agents as a therapeutic aerosol into the thoracic cavity via a nebulizer. Our preliminary study involved nine patients with unresectable pleural mesothelioma (PM) treated with PITAC. Among them, one case was particularly emblematic for demonstrating notable oncological improvements in addition to well-known palliative benefits. This patient underwent two PITAC procedures, one year apart, without perioperative complications. Redo pleural biopsies from both previous and new sites revealed only fibrous tissue and inflammatory cells, with no evidence of malignancy. Beyond achieving pleurodesis, PITAC—by combining cytotoxic and sclerosing effects—may offer effective local antineoplastic control and represent a promising avenue for enhancing loco-regional therapy in PM. Full article

Metachromatic leukodystrophy (MLD) is a rare inherited disorder of lysosomal storage, caused by a deficiency in the arylsulfatase A (ARSA) enzyme, leading to toxic accumulation of sulfatides, which progressively impair motor and cognitive function. MLD is a candidate for inclusion in newborn screening (NBS) programs, due to the narrow pre-symptomatic window for effective therapeutic intervention. We set up a prospective pilot NBS program for MLD in Tuscany, based on a two-step approach. The first-tier test quantified four sulfatides; if levels exceeded the cut-off, we performed the second-tier test by measuring ARSA activity on the same neonatal dried blood spot (DBS). We performed the first-tier test on 42,262 newborns over two years and the second-tier test on residual neonatal DBS from 90 of them (0.21%). We recalled 10 newborns (0.02%) for an additional DBS, due to insufficient residual material for a second-tier test (n = 4) or to low ARSA activity (n = 6). We found normal ARSA activity in all new DBS and identified no new cases of MLD. Retrospective analysis of eight neonatal and fifteen non-neonatal DBS from patients with genetically confirmed MLD showed that the algorithm accurately identified MLD patients. This diagnostic algorithm proved feasible and accurate for early detection of MLD in prospective NBS. Full article

Since ancient times, mushrooms have been considered valuable allies of human well-being both from a dietary and medicinal point of view. Their essential role in several traditional medicines is explained today by the discovery of the plethora of biomolecules that have shown proven efficacy for treating various diseases, including cancer. Numerous studies have already been conducted to explore the antitumoural properties of mushroom extracts against cancer. Still, very few have reported the anticancer properties of mushroom polysaccharides and mycochemicals against the specific population of cancer stem cells (CSCs). In this context, β-glucans are relevant in modulating immunological surveillance against this subpopulation of cancer cells within tumours. Small molecules, less studied despite their spread and assortment, could exhibit the same importance. In this review, we discuss several pieces of evidence of the association between β-glucans and small mycochemicals in modulating biological mechanisms which are proven to be involved with CSCs development. Experimental evidence and an in silico approach are evaluated with the hope of contributing to future strategies aimed at the direct study of the action of these mycochemicals on this subpopulation of cancer cells. Full article

Convolvulus pluricaulis (CP) is a common Indian herb, largely employed in Ayurvedic medicine and known for its neuroprotective and neuroinflammatory action. Its effectiveness against several pathologic/sub-pathologic conditions is widely accepted, but it is not yet completely chemically characterized. In recent years, several researchers have pointed out the involvement of CP and other Convolvulaceae in lipidic and glucidic metabolism, particularly in the control of hyperlipidaemia and diabetic conditions. In this scenario, the aim of the study was to chemically characterize the medium polarity part of the CP whole plant and its fractions and to shed light on their biological activity in adipocyte differentiation using the 3T3-L1 cell model. Our results demonstrated that the CP extract and fractions could upregulate the adipocyte differentiation through the modulation of the nuclear receptor PPARγ (Peroxisome Proliferator-Activated Receptor γ), broadly recognized as a key regulator of adipocyte differentiation, and the glucose transporter GLUT-4, which is fundamental for cellular glucose uptake and for metabolism control. CP also showed the ability to exert an anti-inflammatory effect, downregulating cytokines such as Rantes, MCP-1, KC, eotaxin, and GM-CSF, which are deeply involved in insulin resistance and glucose intolerance. Taken together, these data suggest that CP could exert a potential beneficial effect on glycemia and could be employed as an anti-diabetic adjuvant or, in any case, a means to better control glucose homeostasis. Full article

Wastes and by-products of plant origin are of particular interest to develop a circular economy approach, which attempts to turn them into resources. In this work, thirty-seven neglected plant matrices, including agricultural residues, pest plants, and by-products from the herbal and food industry were extracted and tested for their in vitro anti-tyrosinase, antioxidant, and antibacterial activity against the phytopathogens Pseudomonas syringae pv. syringae ATCC 19310 and Clavibacter michiganensis subsp. nebraskense ATCC 27822. Antioxidant activity ranged from 0.3 to 5 mg of Tr. eq/mL of plant extract, and extract of Castanea sativa pericarp (Csp), Rosa damascena buds (post-distillation) (Rod), and Prunus amygdalus exocarp and mesocarp (Pam) were the most powerful ones. Csp was also capable of inhibiting tyrosinase (IC₅₀ = 16.5 µg/mL), as well as three distillation by-products, namely: Cupressus sempervirens (Css) (IC₅₀ = 95.5 µg/mL), Salvia officinalis (Sco) (IC₅₀ = 87.6 µg/mL), and Helichrysum italicum (Hei) (IC₅₀ = 90.1 µg/mL). Five residues from distillation showed antibacterial activity against C. michiganensis (MICs ranging from 0.125 to 1 mg/mL), namely: Salvia sclarea L. (Sas), Salvia rosmarinus Schleid (Sar), Sco, Hei, and Css. The ¹H NMR fingerprinting of the bioactive matrices was acquired, detecting primary and secondary metabolites (rosmarinic acid, shikimic acid, sclareol, and hydroxycinnamic acids). Full article

Essential oils (EOs) and their vapour phase of Curcuma longa (Zingiberaceae), Cymbopogon citratus (Poaceae), Ocimum campechianum (Lamiaceae), and Zingiber officinale (Zingiberaceae) of cultivated plants grown in an Amazonian Ecuador area were chemically characterised by Gas Chromatography-Flame Ionization Detector (GC-FID), Gas Chromatography–Mass Spectrometry (GC-MS), and Head Space–Gas Chromatograph-Flame Ionization Detector–Mass Spectrometry (HS-GC-FID-MS).figure The EOs analyses led to the identification of 25 compounds for C. longa (99.46% of the total; ar-turmerone: 23.35%), 18 compounds for C. citratus (99.59% of the total; geraniol: 39.43%), 19 compounds for O. campechianum (96.24% of the total; eugenol: 50.97%), and 28 for Z. officinale (98.04% of the total; α-Zingiberene: 15.45%). The Head Space fractions (HS) revealed C. longa mainly characterised by limonene and 1,8-cineole (37.35%) and α-phellandrene (32.33%); Z. officinale and C. citratus showed camphene (50.39%) and cis-Isocitral (15.27%) as the most abundant compounds, respectively. O. campechianum EO revealed a higher amount of sesquiterpenes (10.08%), mainly characterised by E-caryophyllene (4.95%), but monoterpene fraction remained the most abundant (89.94%). The EOs were tested for antioxidant, antimicrobial, and mutagen-protective properties and compared to the Thymus vulgaris EO as a positive reference. O. campechianum EO was the most effective in all the bioactivities checked. Similar results emerged from assaying the bioactivity of the vapour phase of O. campechianum EO. The antioxidant and antimicrobial activity evaluation of O. campechianum EO were repeated through HP-TLC bioautography assay, pointing out eugenol as the lead compound for bioactivity. The mutagen-protective evaluation checked through Ames’s test properly modified evidenced a better capacity of O. campechianum EO compared with the other EOs, reducing the induced mutagenicity at 0.1 mg/plate. However, even with differences in efficacy, the overall results suggest important perspectives for the functional use of the four studied EOs. Full article

Background: The diagnosis of COPD is based on both clinical signs and functional tests. Although there are different functional tests used to assess COPD, no reliable biomarkers able to provide information on pathogenesis and severity are available. The aim of the present study is to explore the relationship between surfactant protein B (Sp-B) serum levels and clinical, radiological, and functional pulmonary parameters in COPD patients. Methods: Forty COPD patients and twenty smokers without airflow limitations or respiratory symptoms were enrolled. Each patient was given questionnaires (CAT and mMRC) and 6MWT, spirometry, DLCO, and computer tomography (CT) were performed. All participants underwent a venous blood sample drawing, and quantitative detection of their Sp-B plasma levels was performed by an enzyme-linked immunosorbent assay. The spirometry and Sp-B plasma levels were assessed after 12 months. Results: A statistically significant difference was found in the plasma Sp-B levels between COPD patients compared to the other group (4.72 + 3.2 ng/mL vs. 1.78 + 1.5 ng/mL; p < 0.001). The change in FEV1 after 12 months (Delta FEV1) showed a significantly negative correlation with respect to the change in Sp-B levels (Delta SpB) (r = −0.4; p < 0.05). This correlation indicates that increasing the plasma dosage of SpB is a foretoken of functional decline. Conclusions: SpB may be considered as a useful marker in COPD assessment and provides prognostic information on lung functional decline. Despite its usefulness, further studies are needed to define its reliability as a biomarker. Full article

Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries. In the present study, we investigated whether the standardized ethanolic extract of A. leucotrichus fruits and R-perillaldehyde, a monoterpenoid isolated from A. leucotrichus fruits, are able to affect different processes involved in different phases of cancer development. In particular, we explored their genoprotective, proapoptotic, antiproliferative, and cytodifferentiating potential on different human cell models. We analyzed the genoprotective and proapoptotic activity on human lymphoblast cells (TK6) using the micronucleus test, and the cytodifferentiation effects on human promyelocytic cells (HL60) through the evaluation of different markers of differentiation forward granulocytes or monocytes. The results showed that the extract and perillaldehyde were able to induce apoptosis and protect from clastogen-induced DNA damage. To our best knowledge, this is the first report on the ability of A. leucotrichus and perillaldehyde to induce apoptosis and protect DNA from the toxicity of different compounds. Data reported in this work are the starting point for their pharmacological use. Going forward, efforts to determine their effects on other events associated with cancer development, such as angiogenesis and metastasization, will provide important information and improve our understanding of their potential in cancer therapy. Full article

The TP53 tumor suppressor gene is known as the guardian of the genome, playing a pivotal role in controlling genome integrity, and its functions are lost in more than 50% of human tumors due to somatic mutations. This percentage rises to 90% if mutations and alterations in the genes that code for regulators of p53 stability and activity are taken into account. Renal cell carcinoma (RCC) is a clear example of cancer that despite having a wild-type p53 shows poor prognosis because of the high rate of resistance to radiotherapy or chemotherapy, which leads to recurrence, metastasis and death. Remarkably, the fact that p53 is poorly mutated does not mean that it is functionally active, and increasing experimental evidences have demonstrated this. Therefore, RCC represents an extraordinary example of the importance of p53 pathway alterations in therapy resistance. The search for novel molecular biomarkers involved in the pathways that regulate altered p53 in RCC is mandatory for improving early diagnosis, evaluating the prognosis and developing novel potential therapeutic targets for better RCC treatment. Full article

(1) Background: Sarcopenia is associated with poor survival and treatment outcomes in several human cancers. The aim of the study was to investigate the prevalence of sarcopenia in a cohort of 58 Caucasian patients with advanced thyroid cancer before and during TKI treatment. The impact of this condition on the outcome of patients was also evaluated. (2) Methods: Sarcopenia was evaluated using the Skeletal Muscle Index (SMI). (3) Results: Pre-treatment sarcopenia was found in 20.7% of patients and this condition significantly affected treatment outcome, emerging as the parameter that has the greatest impact on Progression Free Survival (PFS) (HR 4.29; 95% CI, 1.21–15.11, p = 0.02). A significant reduction in SMI values was observed 3 (p = 0.002) and 12 months (p < 0.0001) after TKI treatment. At a 12-month follow-up, sarcopenia prevalence increased up to 38.5%. Here, 12-month sarcopenia was predicted by a lower SMI (p = 0.029), BMI (p = 0.02) and weight (p = 0.04) and by the presence of bone metastases (p = 0.02). (4) Conclusions: This is the first study that evaluated sarcopenia prevalence and its change over time in Caucasian patients with advanced thyroid cancer under TKI therapy. Sarcopenia seems to be a prognostic factor of TKI treatment outcome, suggesting the importance of the assessment of the nutritional status and body composition in advanced thyroid cancer patients. Full article

The ethnobotany of the Sahrawi people considers various species of plants and crude drugs as food, cooking spices and traditional health remedies. From among these, the fruits of Ammodaucus leucotrichus Coss. & Dur. (Apiaceae), known as Saharan cumin, were chosen for our research. The present paper reports a proximate composition and mineral element analysis of various samples of A. leucotrichus fruits, collected during the balsamic period (full fruiting) from plants grown in Bir Lehlu (Western Sahara) and purchased in a local market (Tindouf). These analyses pointed out interesting nutritional values of the crude drug. Decoction and alcoholic extract, analyzed by HPLC-DAD, evidenced ammolactone-A and R-perillaldehyde as the two main isolated constituents, particularly in the ethanolic extracts (ammolactone-A, market sample: 51.71 ± 0.39 mg/g dry extract; wild sample: 111.60 ± 1.80 mg/g dry extract; R-perillaldehyde, market sample: 145.95 ± 0.35 mg/g dry extract; wild sample: 221.40 ± 0.30 mg/g dry extract). The essential oils, obtained through hydrodistillation, were characterized by GC-MS and evidenced R-perillaldehyde (market sample: 53.21 ± 1.52%; wild sample: 74.01 ± 1.75%) and limonene (market sample: 35.15 ± 1.68%; wild sample: 19.90 ± 1.86%) as the most abundant compounds. The R configuration of perillaldehyde was ascertained and a complete description of the ¹H and ¹³C NMR spectra of ammolactone-A was performed. Full article

Phytopathogenic fungi are among the main causes of productivity losses in agriculture. To date, synthetic chemical pesticides, such as hydroxyanilides, anilinopyrimidines and azole derivatives, represent the main treatment tools for crop plant defence. However, the large and uncontrolled use of these substances has evidenced several side effects, namely the resistance to treatments, environmental damage and human health risks. The general trend is to replace chemicals with natural molecules in order to reduce these side effects. Moreover, the valorisation of agri-food industry by-products through biotransformation processes represents a sustainable alternative to chemical synthesis in several sectors. This research is aimed at comparing the anti-phytopathogenic activity of waste bovine and porcine bile with secosteroids obtained by biotransformation of bile acids with Rhodococcus strains. The ultimate goal is to apply these natural products on food crops affected by phytopathogenic fungi. Full article

The objective of this study was to identify prognostic factors for children and adolescents with relapsed or progressive classical Hodgkin’s lymphoma (cHL) to design salvage therapy tailored to them. We analyzed a homogeneous pediatric population, diagnosed with progressive/relapsed cHL previously enrolled in two subsequent protocols of the Italian Association of Pediatric Hematology and Oncology in the period 1996–2016. There were 272 eligible patients, 17.5% of treated patients with cHL. Overall survival (OS) and event-free survival (EFS) after a 10-year follow-up were 65.3% and 53.3%, respectively. Patients with progressive disease (PD), advanced stage at recurrence, and ≥5 involved sites showed a significantly worse OS. PD, advanced stage, and extra-nodal involvement at recurrence were significantly associated with a poorer EFS. Multivariable analysis identified three categories for OS based on the type of recurrence and number of localizations: PD and ≥5 sites: OS 34%; PD and <5 sites: OS 56.5%; relapses: OS 73.6%. Four categories were obtained for EFS based on the type of recurrence and stage: PD and stage 3–4: EFS 25.5%; PD and stage 1–2: EFS 43%; relapse and stage 3–4: EFS 55.4%; relapse and stage 1–2: EFS 72.1%. Patients with PD, in advanced stage, or with ≥5 involved sites had a very poor survival and they should be considered refractory to first- and second-line standard chemotherapy. Probably, they should be considered for more innovative approaches since the first progression. Conversely, patients who relapsed later with localized disease had a better prognosis, and they could be considered for a conservative approach. Full article

Lissencephaly describes a group of conditions characterized by the absence of normal cerebral convolutions and abnormalities of cortical development. To date, at least 20 genes have been identified as involved in the pathogenesis of this condition. Variants in CEP85L, encoding a protein involved in the regulation of neuronal migration, have been recently described as causative of lissencephaly with a posterior-prevalent involvement of the cerebral cortex and an autosomal dominant pattern of inheritance. Here, we describe a 3-year-old boy with slightly delayed psychomotor development and mild dysmorphic features, including bitemporal narrowing, protruding ears with up-lifted lobes and posterior plagiocephaly. Brain MRI at birth identified type 1 lissencephaly, prevalently in the temporo–occipito–parietal regions of both hemispheres with “double-cortex” (Dobyns’ 1–2 degree) periventricular band alterations. Whole-exome sequencing revealed a previously unreported de novo pathogenic variant in the CEP85L gene (NM_001042475.3:c.232+1del). Only 20 patients have been reported as carriers of pathogenic CEP85L variants to date. They show lissencephaly with prevalent posterior involvement, variable cognitive deficits and epilepsy. The present case report indicates the clinical variability associated with CEP85L variants that are not invariantly associated with severe phenotypes and poor outcome, and underscores the importance of including this gene in diagnostic panels for lissencephaly. Full article

This Randomized Controlled Trial [(RCT) aims to evaluate the effectiveness of a brief Acceptance and Commitment Therapy (ACT)-based intervention combined with treatment as usual (TAU) compared to TAU only in improving psychological conditions in a sample of adolescents with obesity (body mass index, BMI > 97th percentile for age and sex) within the context of a wider multidisciplinary rehabilitation program for weight loss. Fifty consecutive adolescents (12–17 years) of both genders with obesity will be recruited among the patients hospitalized in a clinical center for obesity rehabilitation and randomly allocated into two experimental conditions: ACT + TAU vs. TAU only. Both groups will attend a three-week in-hospital multidisciplinary rehabilitation program for weight loss. The ACT + TAU condition comprises a psychological intervention based on ACT combined with a standard psychological assessment and support to the hospitalization. The TAU comprises the standard psychological assessment and support to the hospitalization. At pre- to post-psychological intervention, participants will complete the Avoidance and Fusion Questionnaire for Youth, the Psychological Well-Being Scale, the Depression Anxiety Stress Scale, the Difficulties in Emotion Regulation Scale, and the Emotional Eating subscale of the Dutch Eating Behavior Questionnaire to assess psychological well-being as the primary outcome and experiential avoidance, psychological distress, emotional dysregulation, and emotional eating as secondary outcomes. Repeated-measures ANOVAs (2 × 2) will be conducted. The study will assess the effectiveness of a brief ACT-based intervention for adolescents with obesity in improving their psychological conditions by targeting specific core processes of the ACT framework (openness, awareness, and engagement). Future directions of the study will assess whether these psychological processes will contribute to addressing long-term weight loss. Full article