•DNA metabarcoding can be applied to forensic fungal samples.•Environmental fungi are informative for the provenance of samples.•Alpha and beta-diversity analysis can support operators in sample ...discrimination.
Metabarcoding through Next Generation Sequencing (NGS) has revolutionized environmental biological studies. The availability of this technical approach has opened the opportunity for a systematic implementation of fungal metabarcoding analysis in forensics, where standardized, sensitive and reproducible protocols are highly desirable. In the present paper, a pipeline including a semi-automated molecular protocol and user-friendly bioinformatics tools are applied to several kinds of environmental samples and forensic caseworks. The identification of fungi that characterize specific environments (like Aspergillus for indoor walls, or Penicillium, Debaryomices and Wickerhamomyces for food storage) can be informative for the provenance of samples. In some situations, fungal analysis cannot allow the identification of a defined environment but seems useful to cluster samples with similar provenance. Based on these considerations, fungal analysis can be included in a wider process of non-human DNA identification in order to provide clues on sample provenance.
An innovative hyaluronan-based nano-delivery system is proposed for the active targeting towards ER+ breast cancer. Hyaluronic acid (HA), an endogenous and bioactive anionic polysaccharide, is ...functionalized with estradiol (ES), a sexual hormone involved in the development of some hormone-dependent tumors, to give an amphiphilic derivative (HA-ES) able to spontaneously self-assemble in water to form soft nanoparticles or nanogels (NHs). The synthetic strategy used to obtain the polymer derivatives and the physico-chemical properties of the obtained nanogels (ES-NHs) are reported. ES-NHs ability to entrap hydrophobic molecules has also been investigated, by loading curcumin (CUR) and docetaxel (DTX), both able to inhibit the growth of ER+ breast cancer. The formulations are studied for their capability to inhibit the growth of the MCF-7 cell line, thus evaluating their efficacy and potential as a selective drug delivery systems. Our results demonstrate that ES-NHs have not toxic effects on the cell line, and that both ES-NHs/CUR and ES-NHs/DTX treatments inhibit MCF-7 cell growth, with ES-NHs/DTX effect higher than that of free DTX. Our findings support the use of ES-NHs to deliver drugs to ER+ breast cancer cells, assuming a receptor-dependent targeting.
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The relevant age-related changes in male body composition are mainly related to the progressive decrease in the level of circulating anabolic hormones, among which testosterone (T) is rather ...important. Its decline, between the ages of 35 and 75, is associated to a loss of muscle mass and fibers number, a doubling of fat mass and a decrease in bone mineral density by 0.3% per yr after age 35; thus the relationship between age-related changes in body composition and T bioactivity reflects an important endocrine aspect of the aging male. The assessment of human body composition and in particular the evaluation of fat tissue and its distribution, is currently standardized by the use of dual-energy x-ray absorpiometry (DXA). In the present paper we review the mechanisms through which testosterone may inhibit adipogenesis, restore the myogenic programme enhancing the protein turnover at muscle level and maintain bone mineral density in elderly men.
OBJECTIVE
Androgens are essential in the maintenance of nitric oxide‐mediated erectile activity in the rat. The objective of the present study was to investigate the role of androgens in regulating ...trabecular smooth muscle relaxation in the corpus cavernosum in response to vasoactive challenge in men with erectile dysfunction (ED).
DESIGN
Retrospective, double‐blind correlation analyses.
PATIENTS
Fifty‐two impotent patients without confounding risk factors for ED were obtained from a total of 250 undergoing diagnostic evaluation.
MEASUREMENTS
All patients had dynamic colour duplex ultrasound (D‐CDU) and hormonal evaluation for LH, total and free testosterone, SHBG and oestradiol.
RESULTS
Based upon D‐CDU results patients were diagnosed as having arteriogenic (AR, n = 18; mean age 51) or corporeal venocclusive (CVO, n = 13; mean age 49) ED; in other patients (n = 21, mean age 43) a diagnosis of psychogenic (P)‐ED was made by comprehensive psychogenic testing and confirmed by normal D‐CDU results. AR and CVO patients had altered compliance of cavernous arteries recorded by D‐CDU 20–25% lower resistive index (RI) than patients with psychogenic ED, and lower free testosterone (FT) levels than psychogenic patients 42.3 ± 3.5 SE and 49.3 ± 5.2 vs. 75.2 ± 7.6 pmol/l, respectively; P < 0.01. More important, in all patients there was a strong direct correlation between resistive index values and FT levels (r = 0.47, P = 0.002); the relationship was maintained also when adjusted for age, SHBG and oestradiol (r = 0.37, P = 0.02).
CONCLUSIONS
These results indicate that in men with erectile dysfuntion low free testosterone may correlate independently of age with the impaired relaxation of cavernous endothelial and corporeal smooth muscle cells to a vasoactive challenge. These findings give clinical support to the experimental knowledge of the importance of androgens in regulating smooth muscle function in the penis.
This study investigated whether nondipping (defined as a day-night change in blood pressure (BP) <or=0%) could be assumed as a diagnostic index for autonomic neuropathy, and assessed its accuracy in ...discriminating between type I diabetic patients with and without autonomic neuropathy. In 87 type I diabetic patients with normal renal function (age 36+/-11, duration 17+/-9 years, serum creatinine 67.2+/-15.9 micromol/l), four cardiovascular tests and 24-h BP monitoring were performed, and the percentage day-night change (Delta) in systolic (SBP) and diastolic BP (DBP) was calculated. Sixteen patients had DeltaSBP and/or DeltaDBP <or=0%. In a multiple logistic regression with adjustment for sex, age, and body mass index, the odds ratio for having autonomic neuropathy was seven times higher in patients with DeltaSBP <or=0% as opposed to those without (odds ratio 6.97, CI 1.4-34.9, P=0.018). Using Receiver Operating Characteristic (ROC) analysis, DeltaBP showed an acceptable accuracy in discriminating between patients with and without autonomic neuropathy (area under the ROC curve 0.69+/-0.06 and 0.72+/-0.05 for DeltaSBP and DeltaDBP, respectively). Adequate cutoff values were 0% for DeltaSBP (sensitivity, 26%; specificity, 95%; positive predictive value, 87%) and 5% for DeltaDBP (sensitivity, 26%; specificity, 92%; positive predictive value, 81%). In type I diabetic patients with normal renal function, a value of DeltaSBP <or=0% identifies the presence of autonomic neuropathy with a very high chance. Nondipping at the cutoff proposed could be considered an adjunctive marker of autonomic neuropathy provided with a high specificity and low sensitivity.
Dipeptidyl peptidase 4 (DPP-4) inhibitors are a new pharmacological class of drugs for treating Type 2 diabetes. They improve the capacity of the organism to control glycemia by increasing the levels ...of active incretins. Their mechanism of action is thus radically different from those of other anti-diabetic drugs currently available. DDP-4 inhibitors use a physiological mechanism to control hyperglycemia, by stimulating the secretion of insulin from beta-cells, decreasing the secretion of glucagon from pancreatic alpha-cells, and at the same time reducing the production of glucose by the liver. DDP-4 inhibitors have shown significant efficacy in maintaining reduced levels of glycosylated hemoglobin for up to 1 year. In vitro and animal studies have shown that they can inhibit apoptosis of beta-cells and favor their regeneration and differentiation. The oral DPP-4 inhibitors vildagliptin, sitagliptin, and saxagliptin are efficacious both alone and in association with other oral anti-diabetic agents and may be administered in a single daily dose. Lastly, they have substantial advantages with respect to other anti-diabetic drugs, since they involve a low risk of hypoglycemia and do not affect body weight.
Employing purified extracellular matrix (ECM) proteins, i.e. type I, III, IV and V collagens (CI, CHI, CIV, CV), laminin (LM) and fibronectin (FN), as antigen sources we detected autoantibodies to ...conformational and/or denatured ECM antigens among 34 of 50 sera obtained from Hashimoto's thyroiditis (HT) patients and 6 of 51 control sera obtained from non-autoimmune thyroid disease patients and healthy donors (HT sera vs. control sera p=4×10−9). Reactivity to conformational antigens, mostly due to autoantibodies of the IgG isotype, was observed in 30/50 HT sera and in 6/51 control sera (p=3.5×10−7) and was not always concomitant with that to linear antigens, found in 23/50 HT and in 6/51 control sera (p=1.6×10−4). Ultrastructural analysis of skin biopsies obtained from 18 HT patients without symptomatic cutaneous diseases revealed defects of the stratified squamous epithelium basement membrane in 11/18, alterations of the stroma in 13/18 and both basement membrane and stromal defects in 9/18. Interestingly, 13/13 (p=0.012) and 9/11 (p=0.012) patients with stromal and basement membrane defects respectively, exhibited serum antibodies to at least one ECM antigen involved in the organization of the altered tissue compartment. Lastly, 10/18 skin biopsies presented immunoglobulin (Ig) and/or complement (C3) deposits along the cutaneous basement membrane zone (BMZ) or in the papillary dermis and 9/10 sera from the same patients simultaneously showed antibodies to at least one ECM antigen involved in the organization of these two skin compartments. Besides, 8/11 HT patients with basement membrane defects exhibited Ig or C3 deposits along the BMZ. Our findings suggest that autoantibodies to ECM molecules might contribute to the development of asymptomatic extra-thyroid skin diseases in HT patients.
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