387 research outputs found
Biodegradable nanofibrous scaffolds as smart delivery vehicles for amino acids
The encapsulation of amino acids (AAs) and their correct preservation before they are ingested are challenging tasks. Nonpolar (l-alanine and l-phenylalanine), polar (l-cysteine hydrochloride and l-asparagine), and charged (l-lysine hydrochloride and l-aspartic acid) AAs were loaded into biodegradable and nontoxic poly(tetramethylene succinate) (PE44) nanofibers (NFs) with electrospinning. The loading of AAs considerably affected the morphology, topography, thermal properties, and wettability of the PE44 NFs. Furthermore, although the AAs crystallized in a phase separated from the polymeric matrix, the distribution of such crystals changed into PE44 NFs and depended on their chemical nature. Release assays in enzyme-free solutions provided evidence that very significant amounts of AAs were retained in the NFs after 7 days, whereas assays in the lipase-containing solution (because lipase performs essential roles in the digestion) showed almost complete release after a few hours. Lipase preferentially attacked the PE44 regions responsible for the retention of AAs in the biphasic system and favored the almost immediate release of the biomolecules. The results displayed in this study, combined with the biocompatibility, biodegradability, and potential use of the PE44 NFs as edible nonnutritional elements, suggest that the loaded PE44âAA NFs could be used to supply essential and conditional AAs.Peer ReviewedPostprint (author's final draft
Bindarit inhibits human coronary artery smooth muscle cell proliferation, migration and phenotypic switching
Bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs) synthesis, reduces neointimal formation in animal models of vascular injury and recently has been shown to inhibit in-stent late loss in a placebo-controlled
phase II clinical trial. However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated. Therefore, we investigated the effect of bindarit on human coronary smooth muscle cells activation, drawing attention to the phenotypic modulation process, focusing on contractile proteins expression as well as proliferation and
migration. The expression of contractile proteins was evaluated by western blot analysis on cultured human coronary smooth muscle cells stimulated with TNF-α (30
ng/mL) or fetal bovine serum (5%). Bindarit (100-300 ”M) reduced the embryonic form of smooth muscle myosin heavy chain while increased smooth muscle α-actin and calponin in both TNF-α- and fetal bovine serum-stimulated cells. These
effects were associated with the inhibition of human coronary smooth muscle cell proliferation/migration and both MCP-1 and MCP-3 production. The effect of
bindarit on smooth muscle cells phenotypic switching was confirmed in vivo in the rat balloon angioplasty model. Bindarit (200 mg/Kg/day) significantly reduced the
expression of the embryonic form of smooth muscle myosin heavy chain, and increased smooth muscle α-actin and calponin in the rat carodid arteries subjected to endothelial denudation. Our results demonstrate that bindarit induces the differentiated state of human coronary smooth muscle cells, suggesting a novel underlying mechanisms by which this drug inhibits neointimal
formation
Breast Fistula Repair after Autologous Fat Graft: A Case Report
We report the case of a 55-year-old female patient who attended our clinic for the presence of a scar retraction in the upper pole of the left breast as a complication of breast augmentation. In the scar area, we observed an orifice that probing revealed to be a fistula. The patient was referred to surgical intervention under general anesthesia to obtain scar contracture release using autologous fat graft; one month after autologous fat injection, following healing of the fistula, the patient underwent a second surgical procedure to replace the left breast implant.
Unexpectedly, two weeks after the surgical procedure, complete healing of the breast fistula within the scar area was observed; this observation was confirmed during the second surgical step for left breast implant repositioning, when we observed the absence of the fistula orifice in the breast implant cavity. Upon clinical examination at 1-year followup, tissue integrity was preserved. The patient's satisfaction was excellent. We have observed a possible additional effect of fat graft
The Potential Role of Pharmacogenomic and Genomic in the Adjuvant Treatment of Early Stage Non Small Cell Lung Cancer
Although notable progress has been made in the treatment of non-small-cell lung cancer (NSCLC) in recent years, this disease is still associated with a poor prognosis. Despite early-stage NSCLC is considered a potentially curable disease following complete resection, the majority of patients relapse and eventually die after surgery. Adjuvant chemotherapy prolongs survival, altough the absolute improvement in 5-year overall survival is only approximately 5%
Sisters acts: converging signaling between CaMKII and CaMKIV, two members of the same family
Calcium (Ca2+
) is a universal second
messenger that regulates a number of diverse cellular
processes including cell proliferation, development,
motility, secretion, learning and memory1, 2. A variety of
stimuli, such as hormones, growth factors, cytokines, and
neurotransmitters induce changes in the intracellular
levels of Ca2+. The most ubiquitous and abundant protein
that serves as a receptor to sense changes in Ca2+
concentrations is Calmodulin (CaM), thus mediating the
role as second messenger of this ion. The Ca2+/CaM
complex initiates a plethora of signaling cascades that
culminate in alteration of cell functions. Among the many
Ca2+/CaM binding proteins, the multifunctional protein
kinases CaMKII and CaMKIV play pivotal roles in the
cell
Candida Biofilm Eye Infection: Main Aspects and Advance in Novel Agents as Potential Source of Treatment
Abstract: Fungi represent a very important cause of microbial eye infections, especially in tropical
and developing countries, as they could cause sight-threating disease, such as keratitis and ocular
candidiasis, resulting in irreversible vision loss. Candida species are among the most frequent
microorganisms associated with fungal infection. Although Candida albicans is still the most frequently
detected organism among Candida subspecies, an important increase in non-albicans species has been
reported. Mycotic infections often represent an important diagnostic-clinical problem due to the
difficulties in performing the diagnosis and a therapeutic problem due to the limited availability
of commercial drugs and the difficult penetration of antifungals into ocular tissues. The ability
to form biofilms is another feature that makes Candida a dangerous pathogen. In this review, a
summary of the state-of-the-art panorama about candida ocular pathology, diagnosis, and treatment
has been conducted. Moreover, we also focused on new prospective natural compounds, including
nanoparticles, micelles, and nanocarriers, as promising drug delivery systems to better cure ocular
fungal and biofilm-related infections. The effect of the drug combination has also been examined
from the perspective of increasing efficacy and improving the course of infections caused by Candida
which are difficult to fight
Breast cancer chemotherapeutic options: a general overview on the preclinical validation of a multi-target ruthenium(III) complex lodged in nucleolipid nanosystems
In this review we have showcased the preclinical development of original amphiphilic
nanomaterials designed for rutheniumâbased anticancer treatments, to be placed within the current
metallodrugs approach leading over the past decade to advanced multitarget agents endowed with
limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC)
interventions, including the tripleânegative subtype (TNBC) with poor therapeutic alternatives. BC
is currently the second most widespread cancer and the primary cause of cancer death in women.
Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC
subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced nextgeneration
metallotherapeutics, with NAMIâA and KP1019 as two iconic ruthenium complexes
having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently
conceived and developed into anticancer drugs demonstrating attractive properties. In this field,
we focused on the evaluation of a Ru(III) complexânamed AziRuâincorporated into a suite of both
zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo
targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the
context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways
which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu
inspired by the wellâknown NAMIâA complex, information on nonânanostructured Ruâbased
anticancer agents have been included in a precise manner
Pituitary function and morphology in Fabry disease.
Endocrine abnormalities are known to affect patients with Fabry disease (FD). Pituitary gland theoretically represents an ideal target for FD because of high vascularization and low proliferation rate. We explored pituitary morphology and function in a cohort of FD patients through a prospectic, monocentric study at an Academic Tertiary Center. The study population included 28 FD patients and 42 sex and age-matched normal subjects. The protocol included a contrast enhancement pituitary MRI, the assessment of pituitary hormones, anti-pituitary, and anti-hypothalamus antibodies. At pituitary MRI, an empty sella was found in 11 (39%) FD patients, and in 2 (5%) controls (p < 0.001). Pituitary volume was significantly smaller in FD than in controls (p < 0.001). Determinants of pituitary volume were age and alpha-galactosidase enzyme activity. Both parameters resulted independently correlated at multivariate analysis. Pituitary function was substantially preserved in FD patients. Empty sella is a common finding in patients with FD. The major prevalence in the elderly supports the hypothesis of a progressive pituitary shrinkage overtime. Pituitary function seems not to be impaired in FD. An endocrine workup with pituitary hormone assessment should be periodically performed in FD patients, who are already at risk of cardiovascular complications
Activity of Free and Liposome-Encapsulated Essential Oil from Lavandula angustifolia against Persister-Derived Biofilm of Candida auris
The high virulence of Candida auris, a pathogen fungus considered as a global threat for public health, is due to its peculiar traits such as its intrinsic resistance to conventional antifungals. Its biofilm lifestyle certainly promotes the prolonged survival of C. auris after disinfection or antifungal treatments. In this work, for the first time, we detected persister cells in a biofilm of C. auris in a microwell plate model, following caspofungin treatment. Furthermore, we showed how persisters can progressively develop a new biofilm in situ, mimicking the re-colonization of a surface which may be responsible for recalcitrant infections. Plant-derived compounds, such as essential oils, may represent a valid alternative to combat fungal infections. Here, Lavandula angustifolia essential oil, as free or encapsulated in liposomes, was used to eradicate primary and persister-derived biofilms of C. auris, confirming the great potential of alternative compounds against emergent fungal pathogens. As in other Candida species, the action of essential oils against C. auris involves ROS production and affects the expression of some biofilm-related genes
Promelanogenic Effects by an Annurca Apple-Based Natural Formulation in Human Primary Melanocytes
Introduction
Melanocytes are engaged in synthesis, transport, and release of pigments at the epidermal-melanin units in response to the finely regulated melanogenic pathway. A multifaceted combination of both intrinsic and extrinsic factors â from endocrine and paracrine dynamics to exogenous stimuli such as sunlight and xenobiotics â modulates expression and activity of proteins involved in pigmentation, including the rate-limiting enzyme tyrosinase. As well as playing critical physiological functions comprising skin photoprotection, melanins define hair and skin pigmentation which in turn have impacted considerably to human social communication since time immemorial. Additionally, numerous skin diseases based on pigmentation alterations can have serious public influence. While several melanogenesis inhibitors are already available, the number of melanin activators and tyrosinase stimulators as drug-like agents is still limited.
Methods
To explore the biological effects of an Annurca Apple-based nutraceutical preparation (AMS) on melanin production, experiments in cellular models of human skin were performed. Both primary cultures and co-cultures of epidermal melanocytes (HEMa) and follicular keratinocytes (HHFK) were used.
Results
We show that AMS, by now branded for its cutaneous beneficial effects, induces in total biocompatibility a significant promelanogenic effect in human primary melanocytes. In line, we found melanin cytosolic accumulation consistent with tyrosinase up-regulation.
Conclusion
Disposal of skin pigmenting agents would be attractive for the treatment of hypopigmentation disorders, to postpone skin photoaging or simply for fashion, so that discovery and development of melanogenesis stimulators, especially from natural sources, is nowadays a dynamic area of research
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