Efficacy of a Zn-based metalorganic framework doped with benznidazole on acute experimental Trypanosoma cruzi infection.

Metal-Organic Frameworks (MOFs) have been shown to enhance the activity of encapsulated compounds by facilitating their passage across cell membranes, thereby enabling controlled and selective release. This study investigates the efficacy of BNZ@Zn-MOFs against the acute phase of Trypanosoma cruzi infection in a mouse model. The particles were synthesized by electroelution (EL), doped with BZN via mechanochemistry, and characterized using scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and X-ray diffraction (XRD). BNZ@Zn-MOFs released 80% of the encapsulated BZN within 3 h, demonstrating no cytotoxicity in NIH-3T3 and HeLa cells. Furthermore, in a model of acute experimental T. cruzi-infection in BALB/c mice, the delivery system exhibited antiparasitic activity at a significantly lower BZN concentration compared to free BZN treatment. PCR analysis of treated mice revealed no parasite DNA in their tissues, and hematoxylin-eosin staining showed no apparent damage to tissue architecture. Additionally, serum levels of liver function enzymes remained unchanged, indicating no adverse effects on liver function. This delivery system, utilizing suboptimal BZN doses, enables the preservation of drug activity while potentially facilitating a substantial decrease in side effects associated with Chagas disease treatment.

Prevalence and Antimicrobial Resistance of Listeria monocytogenes in Different Raw Food from Reynosa, Tamaulipas, Mexico.

Listeria (L.) monocytogenes is an opportunistic foodborne pathogen that causes listeriosis in humans and animals, reaching up to 30% case mortality. There are only a few reports in Mexico about the L. monocytogenes strains found in various foods. The aim of this study was to determine the prevalence of L. monocytogenes, serogroups, virulence genes, and antimicrobial resistance in different foods from Reynosa, Tamaulipas, Mexico. L. monocytogenes strains were characterized by microbiological and molecular methods. Susceptibility to 12 antibiotics was determined according to CLSI and EUCAST. A total of 300 samples of seafood, pasteurized and raw milk, cheese, beef, and chicken were collected from supermarkets and retail markets. The presence of L. monocytogenes was detected in 5.6% of the samples. Most strains belonged to serogroups 4b, 4d, and 4e (68.4%). All strains presented a minimum of four virulence genes; the most common were actA, hly, and plcB (92.1%). A high percentage of antimicrobial susceptibility was observed, with resistance only to STX-TMP (78.9%), STR (26.3%), MEM (21.0%), and E (2.6%). These results show that the foods in Reynosa, Tamaulipas, are a reservoir of L. monocytogenes and represent a potential health risk.

The Role of Nicotinic Receptors on Ca2+ Signaling in Bovine Chromaffin Cells.

Chromaffin cells have been used as a physiological model to understand neurosecretion in mammals for many years. Nicotinic receptors located in the cells' membrane are stimulated by acetylcholine, and they participate in the exocytosis of chromaffin granules, releasing catecholamines in response to stress. In this work, we discuss how the participation of nicotinic receptors and the localization of active zones in the borders of the cytoskeleton can generate local calcium signals leading to secretion. We use a computational model of a cytoskeleton cage to simulate Ca2+ levels in response to voltage and acetylcholine pulses. We find that nicotinic receptors are able to enhance the differences between local and average calcium values, as well as the heterogeneous distributions around the active zones, producing a non-linear, highly localized Ca2+ entry that, although consisting of a few ions, is able to improve secretion responses in chromaffin cells. Our findings emphasize the intricate interplay among nicotinic receptors, the cytoskeleton, and active zones within chromaffin cells as an example of Ca2+-dependent neurosecretion in mammals.

Impact of different levels of handling on Solea senegalensis culture: effects on growth and molecular markers of stress.

Aquaculture routine practices may cause stress induction on the fish and compromise their welfare affecting the production. This experiment aimed to evaluate the potential links between handling during culture with stress responses and growth on Senegalese sole (Solea senegalensis). We worked with two fish cohorts in terms of initial body weight and culture stage: Trial 1 included specimens in the fattening stage (226 ± 4.96 g) and Trial 2 animals in the pre-fattening stage (27.20 ± 0.44 g). The tested culture protocol, which lasted 6 and 4 months for Trial 1 and 2, respectively, mainly reduced handling-derived stressors in the experimental tanks via lowering routine samplings to a minimum. This decrease of the handling-derived stress was reflected in both trials with lower concentration of circulating cortisol in blood plasma from the experimental fish when compared to controls. Moreover, the proposed protocol promoted higher growth in the fish cultured in the less disturbing protocol in Trial 2. Higher specific growth rates and mean body weight and length were reported. In order to further explore the potential beneficial effects of our protocol, we studied the musculoskeletal from Trial 2 gene expression of key genes regulating glucocorticoid signaling pathway and apoptosis: glucocorticoid receptors 1 and 2 (gr1, gr2), heat shock protein 90 AA (hsp90aa), and caspase 6 (casp6). In line with the cortisol reduced level in this trial, gr1, hsp90aa, and casp6 genes showed lower expression in the samples coming from the experimental group. The findings of this study provide valuable information to the aquaculture industry for the management of Solea senegalensis stress and welfare.

Tubulin as a potential molecular target for resveratrol in Giardia lamblia trophozoites, in vitro and in silico approaches.

Giardia lamblia is a globally distributed protozoan parasite that causes intestinal disease. Recently, there is an increase in refractory cases of giardiasis to chemotherapeutic agents, and drugs available cause side effects that may limit its use or cause therapeutic non-compliance. Therefore, search for alternative and less harmful drugs to treat giardiasis is an important task. In this sense, resveratrol (RSV) is a polyphenol with a wide range of pharmacological effects such as antimicrobial, anticarcinogenic and antioxidant. The aim of this study was to evaluate the effects of RSV on Giardia lamblia trophozoites in vitro and in silico, focusing on tubulin affectation, a major protein of the Giardia cytoskeleton which participates in relevant processes for cell survival. In vitro determinations showed that RSV inhibits parasite growth and adherence, causes morphological changes, and induces apoptosis-like cell death through tubulin alterations demonstrated by immunolocalization and Western blot assays. Bioinformatic analysis by molecular docking suggested that RSV binds to Giardia tubulin interface heterodimer, sharing binding residues to those reported with depolymerization inhibitors. These findings suggest that RSV affects microtubular dynamics and make it an interesting compound to study for its safety and antigiardiasic potential.

Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolated from Food-Producing Animals in Tamaulipas, Mexico.

Extended-spectrum ß-lactamase (ESBL)-producing E. coli has become an important global problem for the public health sector. This study aims to investigate the E. coli antimicrobial resistance profile among living food-producing animals in Tamaulipas, Mexico. A total of 200 fecal samples were collected from bovines, pigs, chickens and sheep. A total of 5.0% of the strains were phenotypically confirmed as ESBL producers. A high percentage of phenotypic antimicrobial resistance was observed against gentamicin (93.3%), tetracycline (86.6%) and streptomycin (83.3%). The gentamicin-resistant strains showed MDR, distributed among 27 resistance patterns to different antimicrobials. The antimicrobial resistance gene tet(A) was detected in 73.3% of isolates, aadA1 in 60.0% and sul2 in 43.3% of strains. The blaCTX-M gene was found in 23.3% of strains. The virulence gene hlyA was detected in 43.3% of isolates; stx1 and stx2 were not detected in any strain. The phylotyping indicated that the isolates belonged to groups A (33.3%), B1 (16.6%), B2 (40.0%) and D (10.0%). These results show that food-producing animals might be a reservoir of ESBL-producing bacteria and may play a role in their spread.

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Molecular and Antimicrobial Susceptibility Characterization of Escherichia coli Isolates from Bovine Slaughterhouse Process.

Antimicrobials are routinely used in human and veterinary medicine. With repeated exposure, antimicrobials promote antibiotic resistance, which poses a threat to public health. In this study, we aimed to determine the susceptibility patterns, virulence factors, and phylogroups of E. coli isolates during the killing process in a bovine slaughterhouse. We analyzed 336 samples (from water, surfaces, carcasses, and feces), and 83.3% (280/336) were positive for E. coli. The most common phenotypic resistances that we detected were 50.7% (142/280) for tetracycline, 44.2% (124/280) for cephalothin, 34.6% (97/280) for streptomycin, and 36.7% (103/280) for ampicillin. A total of 82.4% of the isolates had resistance for at least one antimicrobial, and 37.5% presented multiresistance. We detected a total of 69 different phenotypic resistance patterns. We detected six other resistance-related genes, the most prevalent being tetA (22.5%) and strB (15.7%). The prevalence values of the virulence genes were 5.4% in hlyA, 1.4% in stx1, and 0.7% in stx2. The frequencies of the pathogenic strains (B2 and D) were 32.8% (92/280) and 67.1% (188/280) as commensals A and B1, respectively. E. coli isolates with pathogenic potential and multiresistance may represent an important source of dissemination and a risk to consumers.

Induction of cytotoxic effects and changes in DNA methylation-related gene expression in a human fibroblast cell line by the metal-organic framework [H2NMe2]3 [Tb(III)(2,6 pyridinedicarboxylate)3] (Tb-MOF).

Lanthanide metal-organic frameworks (lanthanide MOFs) may be utilized for a variety of environmental and human health applications due to their luminescent properties and high thermal and water stability. However, the cytotoxic and epigenetic effects produced in human cells are not known. Therefore, we evaluated the cytotoxic effects, internalization, and changes in the mRNA abundance of DNA methylation and demethylation enzymes by exposing human fibroblast cells to a metal-organic framework [H2NMe2]3 [Tb(III)(2,6 pyridinedicarboxylate)3] (Tb-MOF). For this purpose, the cells were exposed to six concentrations (0.05 to 1.6 mg/mL) of Tb-MOF for 48 h. Field emission electron microscopy coupled to linear energy dispersive spectroscopy (FESEM‒EDS) and confocal microscopy analysis were performed. The cytotoxicity was determined with crystal violet and MTT assays. The results demonstrated the internalization of Tb-MOF at concentrations as low as 0.05 mg/mL, as well as concentration-dependent toxicity. Additionally, we detected significant changes in the gene expression levels of DNA methyltransferases and demethylases due to the presence of Tb-MOF, suggesting that Tb-MOF could generate epigenetic changes even at low concentrations. The results of our study may establish a foundation for future research attempting to develop and apply secure nanomaterials (e.g., MOFs) to minimize damage to the environment and human health.

Confocal Microscopy Studies of F-Actin Cytoskeleton Distribution and Dynamics Using Fluorescent LifeAct Constructs in Bovine Adrenal Chromaffin Cells.

Cultured bovine chromaffin cells have been characterized as a successful model to study changes in the cytoskeleton during the secretory process. In this sense, the distribution and dynamics of the F-actin cytoskeleton can be studied by confocal microscopy using appropriate molecular tools such as LifeAct, a peptide that stains the structures of F-actin. In this work, we describe some methodological protocols making possible to study, under controlled stimulus conditions, the local dynamic changes of F-actin in the cortical zone and also to detect the simultaneous displacements of chromaffin granules and organelles in active zones.

Genetic Study of SARS-CoV-2 Non Structural Protein 12 in COVID-19 Patients Non Responders to Remdesivir.

Remdesivir (RDV) was the first antiviral drug approved by the FDA to treat severe coronavirus disease-2019 (COVID-19) patients. RDV inhibits SARS-CoV-2 replication by stalling the non structural protein 12 (nsp12) subunit of the RNA-dependent RNA polymerase (RdRp). No evidence of global widespread RDV-resistance mutations has been reported, however, defining genetic pathways to RDV resistance and determining emergent mutations prior and subsequent antiviral therapy in clinical settings is necessary. This study identified 57/149 (38.3%) patients who did not respond to one course (5-days) (n = 36/111, 32.4%) or prolonged (5 to 20 days) (n = 21/38, 55.3%) RDV therapy by subgenomic RNA detection. Genetic variants in the nsp12 gene were detected in 29/49 (59.2%) non responder patients by Illumina sequencing, including the de novo E83D mutation that emerged in an immunosuppressed patient after receiving 10 + 8 days of RDV, and the L838I detected at baseline and/or after prolonged RDV treatment in 9/49 (18.4%) non responder subjects. Although 3D protein modeling predicted no interference with RDV, the amino acid substitutions detected in the nsp12 involved changes on the electrostatic outer surface and in secondary structures that may alter antiviral response. It is important for health surveillance to study potential mutations associated with drug resistance as well as the benefit of RDV retreatment, especially in immunosuppressed patients and in those with persistent replication. IMPORTANCE This study provides clinical and microbiologic data of an extended population of hospitalized patients for COVID-19 pneumonia who experienced treatment failure, detected by the presence of subgenomic RNA (sgRNA). The genetic variants found in the nsp12 pharmacological target of RDV bring into focus the importance of monitoring emergent mutations, one of the objectives of the World Health Organization (WHO) for health surveillance. These mutations become even more crucial as RDV keeps being prescribed and new molecules are being repurposed for the treatment of COVID-19. The present article offers new perspectives for the clinical management of non responder patients treated and retreated with RDV and emphasizes the need of further research of the benefit of combinatorial therapies and RDV retreatment, especially in immunosuppressed patients with persistent replication after therapy.

Transition Metal Complexes with Tridentate Schiff Bases (O N O and O N N) Derived from Salicylaldehyde: An Analysis of Their Potential Anticancer Activity.

Although it is known that the first case of cancer was recorded in ancient Egypt around 1600 BC, it was not until 1917 during the First World War and the development of mustard gas that chemotherapy against cancer became relevant; however, its properties were not recognised until 1946 to later be used in patients. In this sense, the use of metallopharmaceuticals in cancer therapy was extensively explored until the 1960s with the discovery of cisplatin and its anticancer activity. From that date to the present, the search for more effective, more selective metallodrugs with fewer side effects has been an area of continuous exploration. Efforts have led to considering a wide variety of metals from the periodic table, mainly from the d-block, as well as a wide variety of organic ligands, preferably with proven biological activity. In this sense, various research groups have found an ideal binder in Schiff bases, since their raw materials are easily accessible, their synthesis conditions are friendly and their denticity can be manipulated. Therefore, in this review, we have explored the anticancer and antitumor activity reported in the literature for coordination complexes of d-block metals coordinated with tridentate Schiff bases (O N O and O N N) derived from salicylaldehyde. For this work, we have used the main scientific databases CCDC® and SciFinder®.

α3ß4 Acetylcholine Nicotinic Receptors Are Components of the Secretory Machinery Clusters in Chromaffin Cells.

The heteromeric assembly of α3 and ß4 subunits of acetylcholine nicotinic receptors (nAChRs) seems to mediate the secretory response in bovine chromaffin cells. However, there is no information about the localization of these nAChRs in relationship with the secretory active zones in this cellular model. The present work presents the first evidence that, in fact, a population of these receptors is associated through the F-actin cytoskeleton with exocytotic machinery components, as detected by SNAP-25 labeling. Furthermore, we also prove that, upon stimulation, the probability to find α3ß4 nAChRs very close to exocytotic events increases with randomized distributions, thus substantiating the clear dynamic behavior of these receptors during the secretory process. Modeling on secretory dynamics and secretory component distributions supports the idea that α3ß4 nAChR cluster mobility could help with improving the efficiency of the secretory response of chromaffin cells. Our study is limited by the use of conventional confocal microscopy; in this sense, a strengthening to our conclusions could come from the use of super-resolution microscopy techniques in the near future.

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro.

Background: Diarrheal diseases caused by protozoa have a great impact on human health around the world. Giardia lamblia is one of the most common flagellates in the intestinal tract. Factors such as adverse effects to first-line drugs or the appearance of drug-resistant strains, make it necessary to identify new treatment alternatives. Agroindustry waste, like pomegranate peel, are a source of phenolic compounds, which possess antiparasitic activities. In vivo studies demonstrated antigiardiasic potential by reducing cyst shedding and protecting intestinal cells; however, they did not identify the compounds or elucidate any mechanism of action in the parasite. The objective of this study is to identify potential molecular targets and to test the in vitro effects of polyphenols from Punica granatum on Giardia lamblia. Methods: The in vitro antigiardial potential of polyphenolic extract from pomegranate peel (Punica granatum L.) obtained using microwave-ultrasound methodology was evaluated on Giardia lamblia trophozoites. Extract phytochemical identification was performed by HPLC/MS analysis. The effect of polyphenolic extract on growth and adhesion capacity was determined by parasite kinetics; morphological damage was evaluated by SEM, alteration on α-tubulin expression and distribution were analyzed by western blot and immunofluorescence, respectively. Results: The pomegranate peel extract showed the presence of ellagitannins (punicalin and punicalagin, galloyl-dihexahydroxydiphenoyl-hexoside), flavones (luteolin), and ellagic acid, that caused an inhibitory effect on growth and adhesion capacity, particularly on cells treated with 200 µg/mL, where growth inhibition of 74.36%, trophozoite adherence inhibition of 46.8% and IC50 of 179 µg/mL at 48 h were demonstrated. The most important findings were that the extract alters α-tubulin expression and distribution in Giardia trophozoites in a concentration-independent manner. Also, an increase in α-tubulin expression at 200 µg/mL was observed in western blot and diffuse or incomplete immunolabeling pattern, especially in ventral disk. In addition, the extract caused elongation, disturbance of normal shape, irregularities in the membrane, and flagella abnormalities. Discussion: The pomegranate peel extract affects Giardia trophozoites in vitro. The damage is related to the cytoskeleton, due to expression and distribution alterations in α-tubulin, particularly in the ventral disk, a primordial structure for adhesion and pathogenesis. Microtubule impairment could explain morphological changes, and inhibition of adhesion capacity and growth. Besides, this is the first report that suggests that ellagic acid, punicalin, punicalagin and luteolin could be interactioning with the rich-tubulin cytoskeleton of Giardia. Further investigations are needed in order to elucidate the mechanisms of action of the isolated compounds and propose a potential drug alternative for the giardiasis treatment.

Suggestions for Improvements in National Radon Control Strategies of Member States Which Were Developed as a Requirement of EU Directive 2013/59 EURATOM.

Exposure to the indoor air pollutant radon is considered to be a significant health risk globally, as has been demonstrated by many studies over time. A recent WHO statement on radon estimates that, worldwide, approximately 80,000 people may die every year due to lung cancer associated with radon exposure. The recent years have also seen huge improvements in radon policies in European countries, as a consequence of the issuing, in 2013, of the Council Directive 2013/59/Euratom. Although the protection of workers from radon exposure is well established, the protection of the general public needs more improvements. The main objective of this paper is, first, to acknowledge and recognise the improvements in radon protection policies, but also to show that there are many areas where improvements are desirable and possible. The final goal is to suggest better ways to protect the general population from exposure to radon gas. The suggestions are based on the experiences of the co-authors, who come from different disciplines related to radon management. The following fields or areas where improvements are possible are identified: risk communication, building codes, radon policies, including funding, research and protection of children. We describe the work that has been conducted, and the possible improvements and solutions in these fields.

Long-term efficacy and safety profiles following small incision lenticule extraction in eyes with ≥ 5-year follow-up.

PURPOSE: To evaluate long-term efficacy, safety, predictability and stability (refractive and keratometric) of myopic and myopic astigmatism correction with Small Incision Lenticule Extraction (SMILE). METHODS: Single center retrospective review of eyes undergoing SMILE from 2012-2015. Forty-two eyes (23 patients) with ≥ 5-year follow-up. Variables analyzed were preoperative, 3-month, 1-year and last follow-up uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, spherical equivalent (SE) and mean keratometry. Descriptive statistics were performed and results reported following the Standard for Reporting Astigmatism Outcomes. RESULTS: Mean follow-up of 5.98 ± 0.90 years. Mean preoperative SE was -5.26 ± 1.22D (range -2.50 to -8.12D). Mean preoperative cylinder was -0.66 ± 0.61D (range 0.00 to -2.25D). Efficacy and safety indices were 0.86 and 0.98, respectively. In total, 81% of operated eyes achieved an UDVA of ≥ 0.09 logMar (20/25 Snellen). At the last follow-up, ≥1 line of CDVA was gained in 14% of eyes. Five percent lost 1 line of CDVA, and no eye loss ≥2 lines of CDVA. Sixty-nine percent of eyes were within ± 0.50D and 86% within ± 1.00D of the attempted SE correction. Ninety-one percent of eyes had ≤0.50D of postoperative astigmatism and 71% were within ± 15° from the intended correction axis. At the final follow-up, a statistically significant myopic regression of 0.19 ± 0.50D was observed (p = 0.01). CONCLUSIONS: Long-term results demonstrate that SMILE is effective, predictable and safe. SMILE has good stability, low regression compared to LASIK, and no signs of corneal ectasia staging within our standard criteria.

Vesicle Fusion as a Target Process for the Action of Sphingosine and Its Derived Drugs.

The fusion of membranes is a central part of the physiological processes involving the intracellular transport and maturation of vesicles and the final release of their contents, such as neurotransmitters and hormones, by exocytosis. Traditionally, in this process, proteins, such SNAREs have been considered the essential components of the fusion molecular machinery, while lipids have been seen as merely structural elements. Nevertheless, sphingosine, an intracellular signalling lipid, greatly increases the release of neurotransmitters in neuronal and neuroendocrine cells, affecting the exocytotic fusion mode through the direct interaction with SNAREs. Moreover, recent studies suggest that FTY-720 (Fingolimod), a sphingosine structural analogue used in the treatment of multiple sclerosis, simulates sphingosine in the promotion of exocytosis. Furthermore, this drug also induces the intracellular fusion of organelles such as dense vesicles and mitochondria causing cell death in neuroendocrine cells. Therefore, the effect of sphingosine and synthetic derivatives on the heterologous and homologous fusion of organelles can be considered as a new mechanism of action of sphingolipids influencing important physiological processes, which could underlie therapeutic uses of sphingosine derived lipids in the treatment of neurodegenerative disorders and cancers of neuronal origin such neuroblastoma.