20 research outputs found

    Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma

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    Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement

    18, X, Y aneuploidies and transmission electron microscopy studies in spermatozoa from five carriers of different reciprocal translocations

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    6noreservedWe analysed ejaculated spermatozoa from five infertile men with different balanced reciprocal translocations to contribute to the study of meiotic segregation of chromosomes 18, X and Y and also to evaluate sperm morphology by transmission electron microscopy (TEM) analysis. Conventional lymphocyte karyotype analyses highlighted different reciprocal balanced translocations: t(12;13), t(4;9), t(X;8), t(8;10) and t(3;16). Semen analysis was performed by light and TEM. Fluorescence in situ hybridization was performed directly on sperm nuclei using centromeric probes for chromosomes 18, X and Y. The carriers of the balanced reciprocal translocations considered in the present study showed a very similar pattern of sperm pathologies: diffused presence of apoptosis and immaturity. All patients showed meiotic segregation derangements, highlighted by the presence of sperm diploidies and sex chromosome disomies particularly related to the failure of the first meiotic division. However, an increased incidence of chromosome 18 aneuploidy was detected in spermatozoa from t(X;8) and t(8;10) carriers. We have also reported values from sex chromosomes such as t(X;8), although the X chromosome was involved in translocation. Since patients with reciprocal translocations and spermatogenetic impairment are candidates for intracytoplasmic sperm injection cycles, the study of sperm parameters, and particularly of the level of aneuploidy rates, would provide better information for couples at risk and would contribute to the data in the literature for a better understanding of the effects of chromosomal rearrangement on the whole meiotic process and, in particular, on chromosomes not involved in translocation.mixedMoretti, Elena; Pascarelli, N. A.; Giannerini, V.; Geminiani, M.; Anichini, C.; Collodel, GiuliaMoretti, Elena; Pascarelli, N. A.; Giannerini, V.; Geminiani, M.; Anichini, C.; Collodel, Giuli

    Antioxidant effects of potassium ascorbate with ribose therapy in a case with Prader Willi Syndrome

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    Oxidative stress (OS) is involved in several human diseases, including obesity, diabetes, atherosclerosis, carcinogenesis, as well as genetic diseases. We previously found that OS occurs in Down Syndrome as well as in Beckwith-Wiedemann Syndrome (BWS). Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS), a genomic imprinting disorder, characterized by obesity, atherosclerosis and diabetes mellitus type 2, pathologies in which a continuous and important production of free radicals takes place. We verified the presence of OS by measuring a redox biomarkers profile including total hydroperoxides (TH), non protein-bound iron (NPBI), thiols (SH), advanced oxidation protein products (AOPP) and isoprostanes. Thus we introduced in therapy an antioxidant agent, namely potassium ascorbate with ribose (PAR), in addition to GH therapy and we monitored the redox biomarkers profile for four years. A progressive decrease in OS biomarkers occurred until their normalization. In the meantime a weight loss was observed together with a steady growth in standards for age and sex

    Effective Microorganisms and Olive Mill Wastewater Used as Biostimulants to Improve the Performance of <i>Tanacetum balsamita</i> L., a Medicinal Plant

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    The use of biostimulants and/or biofertilizers has acquired considerable importance and can contribute to the sustainable management agriculture, reducing the use of chemical fertilizers, pesticides, and water. This study aims to assess the effects of Effective Microorganisms (EM) and Olive Mill Wastewater (OMW) on the growth, photosynthetic performance and polyphenols content of the medicinal plant Tanacetum balsamita. The EM and OMW were used at two dilution rates. The EM was added to 5% v/v and 10% v/v, while OMW was added to 2.5% v/v and 5% v/v in plants at the early growth stage. After 75 days of treatment, all the treated plants had a leaf number and leaf area almost 2-fold higher than in the Control plants. Moreover, the treatments, at all the concentrations applied had a positive effect on the photosynthetic activity, with an improvement both in terms of the quantum yield of photosynthesis and electrons transport efficiency. The best photosynthetic and growth performances in the treated plants coincided with the higher production of phenolic compounds; indeed, after 75 days, the content of chlorogenic acid, caffeic acid, and isochlorogenic acid was even 2-fold of the Control plants. Also, rutin content was 1.28–1.50-fold respect to the Control extracts. The highest phenolic compound content was reflected by the highest antiradical activity, found in the extracts of the treated plants. The effectiveness of EM to increase the growth and quality of plants and in particular, the potential use of OMW on the cultivated crop was confirmed to this study

    Epilepsy and electroencephalographic anomalies in chromosome 2 aberrations. A review.

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    Epilepsy and electroencephalographic (EEG) anomalies are common in subjects carrying chromosomal aberrations. We report clinical and EEG investigations on 13 patients carrying chromosome 2 anomalies, including two patients with inversions, six with translocations, two with partial duplications and three with interstitial deletion syndromes. Epilepsy and/or EEG anomalies were found in one patient with a chromosome 2 translocation, in both of those carrying partial duplications and in all three with interstitial deletion syndromes. No epilepsy or EEG anomalies were detected in the remaining patients. CONCLUSIONS: Epilepsy may be associated with chromosome 2 aberrations. Gross rearrangements involving the long arm of chromosome 2 might be more often associated with epilepsy than those involving the short arm. The association of epilepsy with chromosome 2 duplications is less clear. In particular, our observations and a review of the literature appear to suggest that a strict relationship between epilepsy and interstitial deletions involving the 2q24-q31 region. In the latter disorder tonic and focal seizures occur early in life. Generalized and focal myoclonic jerks tend to appear in infancy and are subsequently followed by seizures mixed in type. Seizures usually persist up to late childhood and are drug resistant. Further studies are necessary to better define the electroclinical patterns of patients carrying deletions in 2q24-q31. These may help to direct systematic study of this--probably underestimated--cause of severe epileps
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