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Due to its numerous advantages, such as excellent drug accessibility, rapid absorption, and bypass of first-pass metabolism, the route of drug administration that involves crossing the oral mucosa is highly favored. As a result, there is significant interest in investigating the permeability of drugs through this region. The purpose of this review is to describe the various ex vivo and in vitro models used to study the permeability of conveyed and non-conveyed drugs through the oral mucosa, with a focus on the most effective models. Currently, there is a growing need for standardized models of this mucosa that can be used for developing new drug delivery systems. Oral Mucosa Equivalents (OMEs) may provide a promising future perspective as they are capable of overcoming limitations present in many existing models. [ABSTRACT FROM AUTHOR]

Benign prostatic hypertrophy (BPH) is a condition that appears with advancing age and affects 1/3 of men over 50 years, resulting in filling and emptying symptoms. One of the main limitations of endoscopic techniques for BPH is the occurrence of retrograde ejaculation. The purpose of this prospective observational study is to evaluate the efficacy and feasibility of ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP) in the treatment of BPH-related LUTS and the preservation of ejaculation. Sexually active patients with BPH were enrolled and followed up with at 3, 6, and 12 months after surgery. Personal and pharmacological histories were collected, while three standardized questionnaires—the International Index of Erectile Function short form (IIEF-5), the International Consultation on Incontinence Questionnaire for Male Sexual Matters Associated with Lower Urinary Tract Symptoms Module (ICIQ—MLUTSsex), and the International Prostatic Symptom Score (IPSS)—were administered. In addition, all patients underwent uroflowmetry and an assessment of post-void residual volume (PVR). A total of 53 patients were enrolled. A statistically significant improvement in the IPSS score, maximum flow (Qmax), and post-void volume (PVR) at 3 months, 6 months, and 12 months after surgery was found (p < 0.05), while no statistically significant differences were reported between IIEF-5 scores before and after surgery. A total of 48 patients (88.6%) had preserved ejaculation at 3 months, while 92.4% and 94.3% of patients reported preserved ejaculation at 6 and 12 months, respectively. Nevertheless, some degree of hypoposia was referred, at 3, 6, and 12 months, by 43.7%, 30.6%, and 13.2% of patients, respectively. The ES-ThuLEP technique successfully preserved ejaculation in over 90% of patients, representing an ejaculation-sparing alternative in the treatment of BPH. [ABSTRACT FROM AUTHOR]

Athletic performance is influenced by many factors such as the environment, diet, training and endurance or speed in physical effort and by genetic predisposition. Just a few studies have analyzed the impact of genotypes on physical performance in rugby. The aim of this study was to verify the modulation of genetic influence on rugby-specific physical performance. Twenty-seven elite rugby union players were involved in the study during the in-season phase. Molecular genotyping was performed for: angiotensin-converting enzyme (ACE rs4646994), alfa-actinin-3 (ACTN3 rs1815739) and monocarboxylate transporter 1 (MCT1 rs1049434) and their variants. Lean mass index (from skinfolds), lower-limb explosive power (countermovement jump), agility (505), speed (20 m), maximal aerobic power (Yo-yo intermittent recovery test level 1) and repeated sprint ability (12 × 20 m) were evaluated. In our rugby union players ACE and ACTN3 variants did not show any influence on athletic performance. MCT1 analysis showed that TT-variant players had the highest peak vertical power (p = 0.037) while the ones with the AA genotype were the fastest in both agility and sprint tests (p = 0.006 and p = 0.012, respectively). Considering the T-dominant model, the AA genotype remains the fastest in both tests (agility: p = 0.013, speed: p = 0.017). Only the MCT1 rs1049434 A allele seems to be advantageous for elite rugby union players, particularly when power and speed are required. [ABSTRACT FROM AUTHOR]

18β-glycyrrhetinic acid (GA) is a pentacyclic triterpene with promising hepatoprotective and anti-Hepatocellular carcinoma effects. GA low water solubility however reduces its biodistribution and bioavailability, limiting its applications in biomedicine. In this work we used core-shell NPs made of PolyD-L-lactide-co-glycolide (PLGA) coated with chitosan (CS), prepared through an osmosis-based methodology, to efficiently entrap GA. NPs morphology was investigated with SEM and TEM and their GA payload was evaluated with a spectrophotometric method. GA-loaded NPs were administered to HepG2 cells and their efficiency in reducing cell viability was compared with that induced by the free drug in in vitro tests. Cell viability was evaluated by the MTT assay, as well as with Electric Cells-Substrate Impedance Sensing (ECIS), that provided a real-time continuous monitoring. It was possible to correlate the toxic effect of the different forms of GA with the bioavailability of the drug, evidencing the importance of real-time tests for studying the effects of bioactive substances on cell cultures. [ABSTRACT FROM AUTHOR]

Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 μM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is the leading cause of death and disability in people less than 40 years of age in Western countries. Currently, there are no satisfying pharmacological treatments for TBI patients. In this study, we subjected rats to severe TBI (sTBI), testing the effects of a single subcutaneous administration, 30 min post-impact, of a new low molecular weight dextran sulfate, named ILB®, at three different dose levels (1, 5, and 15 mg/kg body weight). A group of control sham-operated animals and one of untreated sTBI rats were used for comparison (each group n = 12). On day 2 or 7 post-sTBI animals were sacrificed and the simultaneous HPLC analysis of energy metabolites, N-acetylaspartate (NAA), oxidized and reduced nicotinic coenzymes, water-soluble antioxidants, and biomarkers of oxidative/nitrosative stress was carried out on deproteinized cerebral homogenates. Compared to untreated sTBI rats, ILB® improved energy metabolism by increasing ATP, ATP/ adenosine diphosphate ratio (ATP/ADP ratio), and triphosphate nucleosides, dose-dependently increased NAA concentrations, protected nicotinic coenzyme levels and their oxidized over reduced ratios, prevented depletion of ascorbate and reduced glutathione (GSH), and decreased oxidative (malondialdehyde formation) and nitrosative stress (nitrite + nitrate production). Although needing further experiments, these data provide the first evidence that a single post-injury injection of a new low molecular weight dextran sulfate (ILB®) has beneficial effects on sTBI metabolic damages. Due to the absence of adverse effects in humans, ILB® represents a promising therapeutic agent for the treatment of sTBI patients. [ABSTRACT FROM AUTHOR]

FOXC2 is a member of the human forkhead-box gene family and encodes a regulatory transcription factor. Mutations in FOXC2 have been associated with lymphedema distichiasis (LD), an autosomal dominant disorder that primarily affects the limbs. Most patients also show extra eyelashes, a condition known as distichiasis. We previously reported genetic and clinical findings in six unrelated families with LD. Half the patients showed missense mutations, two carried frameshift mutations and a stop mutation was identified in a last patient. Here we analyzed the subcellular localization and transactivation activity of the mutant proteins, showing that all but one (p.Y109*) localized to the nucleus. A significant reduction of transactivation activity was observed in four mutants (p.L80F, p.H199Pfs*264, p.I213Tfs*18, p.Y109*) compared with wild type FOXC2 protein, while only a partial loss of function was associated with p.V228M. The mutant p.I213V showed a very slight increase of transactivation activity. Finally, immunofluorescence analysis revealed that some mutants were sequestered into nuclear aggregates and caused a reduction of cell viability. This study offers new insights into the effect of FOXC2 mutations on protein function and shows the involvement of aberrant aggregation of FOXC2 proteins in cell death. [ABSTRACT FROM AUTHOR]

Neutral lipid storage disease with myopathy (NLSDM) and with ichthyosis (NLSDI) are rare autosomal recessive disorders caused by mutations in the PNPLA2 and in the ABHD5/CGI58 genes, respectively. These genes encode the adipose triglyceride lipase (ATGL) and α-β hydrolase domain 5 (ABHD5) proteins, which play key roles in the function of lipid droplets (LDs). LDs, the main cellular storage sites of triacylglycerols and sterol esters, are highly dynamic organelles. Indeed, LDs are critical for both lipid metabolism and energy homeostasis. Partial or total PNPLA2 or ABHD5/CGI58 knockdown is characteristic of the cells of NLSD patients; thus, these cells are natural models with which one can unravel LD function. In this review we firstly summarize genetic and clinical data collected from NLSD patients, focusing particularly on muscle, skin, heart, and liver damage due to impaired LD function. Then, we discuss how NLSD cells were used to investigate and expand the current structural and functional knowledge of LDs. [ABSTRACT FROM AUTHOR]