Corpora amylacea (CA) in the human brain are granular bodies formed by polyglucosan aggregates that amass waste products of different origins. They are generated by astrocytes, mainly during aging ...and neurodegenerative conditions, and are located predominantly in periventricular and subpial regions. This study shows that CA are released from these regions to the cerebrospinal fluid and are present in the cervical lymph nodes, into which cerebrospinal fluid drains through the meningeal lymphatic system. We also show that CA can be phagocytosed by macrophages. We conclude that CA can act as containers that remove waste products from the brain and may be involved in a mechanism that cleans the brain. Moreover, we postulate that CA may contribute in some autoimmune brain diseases, exporting brain substances that interact with the immune system, and hypothesize that CA may contain brain markers that may aid in the diagnosis of certain brain diseases.
Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein ...encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches.
Topical delivery has received great attention due to its localized drug delivery, its patient compliance, and its low risk for side effects. Recent developments have focused on studying new drug ...delivery systems as a strategy for addressing the challenges of current topical treatments. Here we describe the advances on an innovative drug delivery platform called DELOS nanovesicles for topical drug delivery. Previously, the production of DELOS nanovesicles demonstrated potentiality for the topical treatment of complex wounds, achieving well-tolerated liquid dispersions by this route. Here, research efforts have been focused on designing these nanocarriers with the best skin tolerability to be applied even to damaged skin, and on exploring the feasibility of adapting the colloidal dispersions to a more suitable dosage form for topical application. Accordingly, these drug delivery systems have been efficiently evolved to a hydrogel using Methocel
K4M, presenting proper stability and rheological properties. Further, the integrity of these nanocarriers when being gellified has been confirmed by cryo-transmission electron microscopy and by Förster resonance energy transfer analysis with fluorescent-labeled DELOS nanovesicles, which is a crucial characterization not widely reported in the literature. Additionally, in vitro experiments have shown that recombinant human Epidermal Growth Factor (rhEGF) protein integrated into gellified DELOS nanovesicles exhibits an enhanced bioactivity compared to the liquid form. Therefore, these studies suggest that such a drug delivery system is maintained unaltered when hydrogellified, becoming the DELOS nanovesicles-based hydrogels, an advanced formulation for topical use.
Highlights • Molecular autopsy should be implemented in forensic protocols. • Nearly 40% of sudden death young cases carry a cardiac potentially pathogenic variant. • It is crucial to undertake a ...careful genetic analysis in a clinical context. • Genetic analyses help to identify relatives at risk of sudden death.
Display omitted
In this paper, nutriosomes (phospholipid vesicles associated with Nutriose® FM06) were modified to obtain new systems aimed at enhancing the efficacy of curcumin in counteracting ...malaria infection upon oral administration. Eudragit® L100, a pH-sensitive co-polymer, was added to these vesicles, thus obtaining eudragit-nutriosomes, to improve their in vivo performances. Liposomes without eudragit and nutriose were also prepared as a reference. Cryo-TEM images showed the formation of multicompartment vesicles, with mean diameter around 300 nm and highly negative zeta potential. Vesicles were stable in fluids mimicking the gastro-intestinal content due to the high phospholipid concentration and the presence of gastro-resistant eudragit and digestion-resistant nutriose. Eudragit-nutriosomes disclosed promising performances in vitro and in vivo: they maximized the ability of curcumin to counteract oxidative stress in intestinal cells (Caco-2), which presumably reinforced its systemic efficacy. Orally-administered curcumin-loaded eudragit-nutriosomes increased significantly the survival of malaria-infected mice relative to free curcumin-treated controls.
Recurrence of gastric schwannoma Ruiz Pardo, José; Sánchez Fuentes, Pedro Antonio; García Redondo, Manuel ...
Revista española de enfermedades digestivas,
04/2023, Letnik:
115, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Gastric schwannoma can be malignant in 13.8% of cases. The prognosis of malignant schwannoma is usually poor, characterized by a rapidly progressive disease course and a poor response to ...chemotherapy. Normally, the recurrence of schwannoma is due to involvement of the surgical resection margin. In turn, recurrence of malignant gastric schwannoma GS is approximately 50%, 25% locoregional and 25% with liver metastases. Even after a complete gastric resection with associated lymphadenectomy, schwannoma may present liver metastases during follow-up.
Streptococcus constellatus is a Gram-positive commensal bacterium of the oropharyngeal, gastrointestinal and urogenital flora. It can cause abscesses in different parts of the body, especially in ...immunocompromised patients. We present the clinical case of a 33-year-old female patient with a previous history of one anastomosis gastric bypass, among others. The patient was hospitalized two years after surgery for peritonitis secondary to a perforation in the biliopancreatic loop, underwent laparoscopic surgery and was hospitalised for two weeks. Fifteen days after being discharged from the hospital, she went to the emergency service for abdominal pain and fever. An abdominal and pelvic computerized tomography (CT) scan showed a multiloculated pelvic collection with thickened and hypercapillary walls.
An analysis of the prognostic impact of up to 36 immuno-inflammatory indices at 3 different times during the diagnostic-therapeutic process for gastric cancer. The dependent variable was disease-free ...survival at 3 years. The independent factors obtained were combined with TNM to provide an improved prognostic model.
PDF
