RESUMEN
T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanism by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200-nm pores but not in 400-nm pores. Consequently, formation of TCR nanoclustered hotspots within 200-nm pores allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.
Asunto(s)
Expresión Génica/inmunología , Activación de Linfocitos/inmunología , Microvellosidades/inmunología , Linfocitos T/inmunología , Actinas/inmunología , Células Presentadoras de Antígenos/inmunología , Células Cultivadas , Humanos , Receptores de Antígenos de Linfocitos T/inmunología , Transducción de Señal/inmunologíaRESUMEN
The current era of cancer research has been continuously advancing upon identifying novel aspects of tumorigenesis and the principal mechanisms behind the unleashed proliferation, invasion, drug resistance and immortality of cancer cells in hopes of exploiting these findings to achieve a more effective treatment for cancer. In pursuit of this goal, the identification of the first components of an extremely important regulatory pathway in Drosophila melanogaster that largely determines cell fate during the developmental stages, ended up in the discovery of the highly sophisticated Hippo signaling cascade. Soon after, it was revealed that deregulation of the components of this pathway either via mutations or through epigenetic alterations can be observed in a vast variety of tumors and these alterations greatly contribute to the neoplastic transformation of cells, their survival, growth and resistance to therapy. As more hidden aspects of this pathway such as its widespread entanglement with other major cellular signaling pathways are continuously being uncovered, many researchers have sought over the past decade to find ways of therapeutic interventions targeting the major components of the Hippo cascade. To date, various approaches such as the use of exogenous targeting miRNAs and different molecular inhibitors have been recruited herein, among which naturally occurring compounds have shown a great promise. On such a basis, in the present work we review the current understanding of Hippo pathway and the most recent evidence on targeting its components using natural plant-derived phytochemicals.
Asunto(s)
Drosophila melanogaster , Neoplasias , Animales , Transformación Celular Neoplásica , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Vía de Señalización Hippo , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Proteínas Serina-Treonina Quinasas , Transducción de Señal/genéticaRESUMEN
OBJECTIVES: Rapidly growing evidence suggests that immune cells play a key role in determining tumor progression. Tumor cells are surrounded by a microenvironment composed of different cell populations including immune cells. The cross talk between tumor cells and the neighboring microenvironment is an important factor to take into account while designing tumor therapies. Despite significant advances in immunotherapy strategies, a relatively small proportion of patients have successfully responded to them. Therefore, the search for safe and efficient drugs, which could be used alongside conventional therapies to boost the immune system against tumors, is an ongoing need. In the present work, the modulatory effects of melatonin on different components of tumor immune microenvironment are reviewed. METHODS: A thorough literature review was performed in PubMed, Scopus, and Web of Science databases. All published papers in English on tumor immune microenvironment and the relevant modulatory effects of melatonin were scrutinized. RESULTS: Melatonin modulates macrophage polarization and prevents M2 induction. Moreover, it prevents the conversion of fibroblasts into cancer-associated fibroblasts (CAFs) and prevents cancer cell stemness. In addition, it can affect the payload composition of tumor-derived exosomes (TEXs) and their secretion levels to favor a more effective anti-tumor immune response. Melatonin is a safe molecule that affects almost all components of the tumor immune microenvironment and prevents them from being negatively affected by the tumor. CONCLUSION: Based on the effects of melatonin on normal cells, tumor cells and microenvironment components, it could be an efficient compound to be used in combination with conventional immune-targeted therapies to increase their efficacy.
Asunto(s)
Fibroblastos Asociados al Cáncer , Melatonina , Neoplasias , Humanos , Melatonina/farmacología , Melatonina/uso terapéutico , Fibroblastos/patología , Fibroblastos Asociados al Cáncer/patología , Inmunoterapia , Microambiente TumoralRESUMEN
Circulating tumor cells (CTCs), secreted from primary and metastatic malignancies, hold a wealth of essential diagnostic and prognostic data for multiple cancers. Significantly, the information contained within these cells may hold the key to understanding cancer metastasis, both individually and fundamentally. Accordingly, developing ways to identify, isolate and interrogate CTCs plays an essential role in modern cancer research. Unfortunately, CTCs are typically present in the blood in vanishingly low titers and mixed with other blood components, making their isolation and analysis extremely challenging. Herein, we report the design, fabrication and optimization of a microfluidic device capable of automatically isolating CTCs from whole blood. This is achieved in two steps, via the passive viscoelastic separation of CTCs and white blood cells (WBCs) from red blood cells (RBCs), and subsequent active magnetophoretic separation of CTCs from WBCs. We detail the specific geometries required to balance the elastic and inertial forces required for successful passive separation of RBCs, and the use of computational fluid dynamics (CFD) to optimize active magnetophoretic separation. We subsequently describe the use of magnetic biosilica frustules, extracted from Chaetoceros sp. diatoms, to fluorescently tag CTCs and facilitate magnetic isolation. Finally, we use our microfluidic platform to separate HepG2-derived CTCs from whole blood, demonstrating exceptional CTC recovery (94.6%) and purity (89.7%).
RESUMEN
Mesenchymal stem cells (MSCs) are mesenchymal precursors of various origins, with well-known immunomodulatory effects. Natural killer (NK) cells, the major cells of the innate immune system, are critical for the antitumor and antiviral defenses; however, in certain cases, they may be the main culprits in the pathogenesis of some NK-related conditions such as autoimmunities and hematological malignancies. On the other hand, these cells seem to be the major responders in beneficial phenomena like graft versus leukemia. Substantial data suggest that MSCs can variably affect NK cells and can be affected by these cells. Accordingly, acquiring a profound understanding of the crosstalk between MSCs and NK cells and the involved mechanisms seems to be a necessity to develop therapeutic approaches based on such interactions. Therefore, in this study, we made a thorough review of the existing literature on the interactions between MSCs and NK cells with a focus on the underlying mechanisms. The current knowledge herein suggests that MSCs possess a great potential to be used as tools for therapeutic targeting of NK cells in disease context and that preconditioning of MSCs, as well as their genetic manipulation before administration, may provide a wider variety of options in terms of eliciting more specific and desirable therapeutic outcomes. Nevertheless, our knowledge regarding the effects of MSCs on NK cells is still in its infancy, and further studies with well-defined conditions are warranted herein.
Asunto(s)
Comunicación Celular , Células Asesinas Naturales/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/cirugía , Terapia Genética , Humanos , Células Asesinas Naturales/inmunología , Células Madre Mesenquimatosas/inmunología , Neoplasias/inmunología , Neoplasias/metabolismo , Neoplasias/cirugía , Fenotipo , Transducción de Señal , Microambiente TumoralRESUMEN
Melatonin is a ubiquitous indole amine that plays a fundamental role in the regulation of the biological rhythm. Disrupted circadian rhythm alters the expression of clock genes and deregulates oncogenes, which finally promote tumor development and progression. An evidence supporting this notion is the higher risk of developing malignancies among night shift workers. Circadian secretion of the pineal hormone also synchronizes the immune system via a reciprocal association that exists between the immune system and melatonin. Immune cells are capable of melatonin biosynthesis in addition to the expression of its receptors. Melatonin induces big changes in different immune cell proportions, enhances their viability and improves immune cell metabolism in the tumor microenvironment. These effects might be directly mediated by melatonin receptors or indirectly through alterations in hormonal and cytokine release. Moreover, melatonin induces apoptosis in tumor cells via the intrinsic and extrinsic pathways of apoptosis, while it protectsthe immune cells. In general, melatonin has a profound impact on immune cell trafficking, cytokine production and apoptosis induction in malignant cells. On such a basis, using melatonin and resynchronization of sleep cycle may have potential implications in immune function enhancement against malignancies, which will be the focus of the present paper.
Asunto(s)
Ritmo Circadiano/fisiología , Melatonina/metabolismo , Neoplasias/inmunología , Neoplasias/patología , Microambiente Tumoral/inmunología , Apoptosis/fisiología , Movimiento Celular/fisiología , Citocinas/metabolismo , Exosomas/metabolismo , HumanosRESUMEN
Elastic nature of the viscoelastic fluids induces lateral migration of particles into a single streamline and can be used by microfluidic based flow cytometry devices. In this study, we investigated focusing efficiency of polyethylene oxide based viscoelastic solutions at varying ionic concentration to demonstrate their use in impedimetric particle characterization systems. Rheological properties of the viscoelastic fluid and particle focusing performance are not affected by ionic concentration. We investigated the viscoelastic focusing dynamics using polystyrene (PS) beads and human red blood cells (RBCs) suspended in the viscoelastic fluid. Elasto-inertial focusing of PS beads was achieved with the combination of inertial and viscoelastic effects. RBCs were aligned along the channel centerline in parachute shape which yielded consistent impedimetric signals. We compared our impedance-based microfluidic flow cytometry results for RBCs and PS beads by analyzing particle transit time and peak amplitude at varying viscoelastic focusing conditions obtained at different flow rates. We showed that single orientation, single train focusing of nonspherical RBCs can be achieved with polyethylene oxide based viscoelastic solution that has been shown to be a good candidate as a carrier fluid for impedance cytometry.
Asunto(s)
Citometría de Flujo , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas , Elasticidad , Impedancia Eléctrica , Eritrocitos/citología , Citometría de Flujo/instrumentación , Citometría de Flujo/métodos , Humanos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , ViscosidadRESUMEN
Olanzapine (OLA), is prescribed as an anti-psychotic medicine in schizophrenia patients. In this study, the protective effect of OLA against genotoxicity and apoptosis induced by ionizing radiation in human healthy lymphocytes was evaluated. At first, the antioxidant activities of OLA were assayed by two different methods as free radical scavenging with DPPH (2,2-diphenyl-1-picryl-hydrazyl) and ferric reducing power methods. In in vitro experiment, human blood samples were treated with OLA at various concentrations (0.25-20 µM) for 3 h and then were exposed to X-ray at a dose of 150 cGy. The genotoxicity was assessed in binucleated human lymphocytes with micronuclei assay. The apoptotic lymphocytes were assessed by flow cytometry in OLA treated and/or irradiated lymphocytes. OLA exhibited free radical scavenging and reducing power activities more than ascorbic acid. The results showed that the lymphocytes treated with OLA and later exposed to IR presented lower frequencies of micronuclei and apoptosis compared to the control sample which was irradiated and not treated to OLA. The maximum radioprotection was observed at 20 µM of OLA with 83% of efficacy. The present study suggested the protective role for OLA in protection radiation-induced genetic damage and apoptosis induced by ionizing irradiation in human normal cells.
Asunto(s)
Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Olanzapina/farmacología , Adulto , Apoptosis/efectos de los fármacos , Células Cultivadas , Daño del ADN , Rayos gamma , Voluntarios Sanos , Humanos , Masculino , Olanzapina/efectos de la radiación , Radiación Ionizante , Protectores contra Radiación/farmacología , Rayos XRESUMEN
The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34+ cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34+ and CD34+ CD38- cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1). Moreover, in vivo analysis demonstrates that PD reduces engraftment capacity of ex vivo expanded CD34+ cells. Notably, when ERK pathway is blocked in UCB-MNCs, spontaneous erythroid differentiation is promoted, found in concomitant with increasing number of burst-forming unit-erythroid colony (BFU-E) as well as enhancement of erythroid glycophorin-A marker. These results are in total conformity with up-regulation of some erythroid enhancer genes (TAL1, GATA2, LMO2) and down-regulation of some erythroid repressor genes (JUN, PU1) as well. Taken together, our results support the idea that MEK/ERK pathway has a critical role in achieving the correct balance between self-renewal and differentiation of UCB cells. Also, we suggest that inhibition of ERK signalling could likely be a new key for erythroid induction of UCB-haematopoietic progenitor cells.
Asunto(s)
Benzamidas/farmacología , Difenilamina/análogos & derivados , Células Eritroides/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Animales , Animales Recién Nacidos , Antígenos CD/genética , Antígenos CD/inmunología , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Difenilamina/farmacología , Células Eritroides/citología , Células Eritroides/inmunología , Femenino , Sangre Fetal/citología , Sangre Fetal/inmunología , Factor de Transcripción GATA2/genética , Factor de Transcripción GATA2/inmunología , Regulación de la Expresión Génica , Glicoforinas/genética , Glicoforinas/inmunología , Supervivencia de Injerto , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Humanos , Inmunofenotipificación , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/inmunología , Ratones , Embarazo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/inmunología , Proteína 1 de la Leucemia Linfocítica T Aguda/genética , Proteína 1 de la Leucemia Linfocítica T Aguda/inmunología , Trasplante HeterólogoRESUMEN
The reciprocal interactions of cancer cells with their microenvironment constitute an inevitable aspect of tumor development, progression and response to treatment in all cancers. Such bilateral transactions also serve as the key scenario underlying the development of drug resistance in many cases finally determining the fate of the disease and survival. In this view, a class of extracellular vesicles (EV) known as exosomes (EX) have been shown in the past few years to be important mediators of local and remote cell-to-cell contact changing the activity of their target cells by introducing their content of proteins, non-coding RNAs, and membrane-associated small molecules. In addition to the direct targeting of cancer cells, which has been routinely undertaken by different means to date, parallel attempts to change the signaling network governed by tumor-derived exosomes (TDE) may offer a promising potential to be utilized in cancer therapy. TDE drive diverse functions in the body, most of which have been shown to act to the advantage of tumor progression; however, there are also several studies that report the good aspects of TDE the interruption of which may result in undesirable outcomes. In the present paper, we made an effort to address this important issue by reviewing the very recent literature on different aspects of EX biogenesis and regulation and the various bodily effects of TDE which have been uncovered to date. Moreover, we have reviewed the possible interventions that can be made in TDE release as an important stage of EX biogenesis. Finally, keeping a criticizing view, the advantages and disadvantages of such interventions have been discussed and the future prospect in the field has been outlined.
Asunto(s)
Antineoplásicos/uso terapéutico , Exocitosis/efectos de los fármacos , Exosomas/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/efectos adversos , Exosomas/metabolismo , Exosomas/patología , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Transducción de Señal/efectos de los fármacos , Microambiente TumoralRESUMEN
Melatonin, a pineal indolamine, participates in different body functions and is shown to possess diverse biological activities such as anti-tumor action. Angiogenesis inhibition is one of the mechanisms by which melatonin exerts its oncostatic effects. Increased angiogenesis is a major feature of tumor progression, thus angiogenesis inhibition is a critical step in cancer therapy. Melatonin employs a variety of mechanisms to target nutrients and oxygen supply to cancer cells. At the transcriptional level, hypoxia induced factor-1α (HIF-1α) and the genes under its control, such as vascular endothelial growth factor (VEGF) are the main targets of melatonin for inhibition of angiogenesis. Melatonin prevents translocation of HIF-1α into the nucleus thereby hindering VEGF expression and also prevents the formation of HIF-1α, phospho-STAT3 and CBP/p300 complex which is involved in the expression of angiogenesis-related genes. Angiostatic properties of melatonin could be also due to its ability to inhibit VEGFR2's activation and expression. Other angiostatic mechanisms of melatonin include the inhibition of endothelial cell migration, invasion, and tube formation. In the present study, we have reviewed the molecular anti-angiogenesis pathways mediated by melatonin and the responsible mechanisms in various types of cancers both in vitro and in vivo.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Melatonina/uso terapéutico , Neoplasias/tratamiento farmacológico , Neovascularización Patológica , Proteínas Angiogénicas/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias/irrigación sanguínea , Neoplasias/metabolismo , Neoplasias/patología , Transducción de Señal/efectos de los fármacosRESUMEN
Aluminum phosphide (AlP), one of the most commonly used pesticides worldwide, has been the leading cause of self-poisoning mortalities among many Asian countries. The heart is the main organ affected in AlP poisoning. Melatonin has been previously shown to be beneficial in reversing toxic changes in the heart. The present study reveals evidence on the probable protective effects of melatonin on AlP-induced cardiotoxicity in rats. The study groups included a control (almond oil only), ethanol 5% (solvent), sole melatonin (50 mg/kg), AlP (16.7 mg/kg), and 4 AlP + melatonin groups which received 20, 30, 40 and 50 mg/kg of melatonin by intraperitoneal injections following AlP treatment. An electronic cardiovascular monitoring device was used to record the electrocardiographic (ECG) parameters. Heart tissues were studied in terms of oxidative stress biomarkers, mitochondrial complexes activities, ADP/ATP ratio and apoptosis. Abnormal ECG records as well as declined heart rate and blood pressure were found to be related to AlP administration. Based on the results, melatonin was highly effective in controlling AlP-induced changes in the study groups. Significant improvements were observed in the activities of mitochondrial complexes, oxidative stress biomarkers, the activities of caspases 3 and 9, and ADP/ATP ratio following treatment with melatonin at doses of 40 and 50 mg/kg. Our results indicate that melatonin can counteract the AlP-induced oxidative damage in the heart. This is mainly done by maintaining the normal balance of intracellular ATP as well as the prevention of oxidative damage. Further research is warranted to evaluate the possibility of using melatonin as an antidote in AlP poisoning.
Asunto(s)
Compuestos de Aluminio/toxicidad , Cardiotónicos/farmacología , Cardiotoxicidad/prevención & control , Melatonina/farmacología , Fosfinas/toxicidad , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Cardiotoxicidad/etiología , Cardiotoxicidad/mortalidad , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Adequate daily milk and dairy products intake seems to an important for adolescents' health. This study aimed to identify the high-risk group adolescents who did not meet the recommended daily serving milk and dairy products and indeed to find out associated factors relating to their nutrition behaviors. METHODS: This cross sectional study was carried out on 7th grade students, in Tabriz, East Azerbaijan province, Iran. An anonymous self-administrated questionnaire including items on perceived social support, physical activity, and sedentary behaviors was administered. In addition a valid food frequency questionnaire (FFQ) measuring daily milk products serving intake as a main outcome measure was completed for each respondent. Logistic regression analysis was applied to examine the association between milk and dairy products consumption and independents variables. RESULTS: In all 402 students (51.5 % female) participated in the study. The mean age of students was 12.9 (SD = 0.49) years. The average daily intake of milk and dairy products was 1.64 (SD = 0.78) servings per day. Overall 14.2 % of adolescents (18.8 % of girls, and 9.2 % of boys, p = 0.006) reported consumption of the recommended daily milk and dairy products serving per day. The results indicated that gender boys (OR for boys = 2.41, 95 % CI = 1.25-4.67), mother age (OR for age group 40-55 years = 2.52, 95 % CI = 1.18-5.38), poor perceived emotional family support, (OR = 1.10, 95 % CI = 1.05-3.61), and poor perceived practical family support (OR = 2.04, 95 % CI = 1.18-4.17) were the most significant contributing factors to low level milk and dairy products intake in adolescents. CONCLUSION: The findings indicated that adolescents did not take the recommended daily amount of milk and dairy products and this appeared to be strongly related to low perceived family support. To achieve the recommended daily milk and dairy products serving consumption, family involvements in any programs that specifically address emotional and practical support for promoting daily milk and dairy products intake among adolescents are suggested.
Asunto(s)
Conducta Alimentaria/psicología , Educación en Salud/organización & administración , Promoción de la Salud/organización & administración , Leche/estadística & datos numéricos , Apoyo Social , Adolescente , Conducta del Adolescente/psicología , Fenómenos Fisiológicos Nutricionales de los Adolescentes , Animales , Estudios Transversales , Femenino , Humanos , Irán , Masculino , Oportunidad Relativa , Encuestas y CuestionariosRESUMEN
BACKGROUND: Following the implementation of family physician program in 2004 in Iranian healthcare system, the understanding in changes in physicians' practice has become important. OBJECTIVE: The objective of this study was to determine the level of family physicians' job satisfaction and its relationship with their performance level. MATERIALS AND METHODS: A cross-sectional study was conducted among all 367 family physicians of East Azerbaijan province in during December 2009 to May 2011 using a self-administered, anonymous questionnaire for job satisfaction. The performance scores of primary care physicians were obtained from health deputy of Tabriz Medical University. RESULTS: In this study, overall response rate was 64.5%. The average score of job satisfaction was 42.10 (±18.46), and performance score was 87.52 (±5.74) out of 100. There was significant relationships between working history and job satisfaction (P = 0.014), marital status (P = 0.014), and sex (P = 0.018) with performance among different personal and organizational variables. However, there was no significant relationship between job satisfaction and performance, but satisfied people had about three times better performance than their counterparts (all P < 0.05). CONCLUSIONS: The low scores of family physicians in performance and job satisfaction are obvious indications for more extensive research in identifying causes and finding mechanisms to improve the situation, especially in payment methods and work condition, in existing health system.
Asunto(s)
Evaluación del Rendimiento de Empleados/normas , Reforma de la Atención de Salud , Satisfacción en el Trabajo , Médicos de Atención Primaria/psicología , Médicos de Atención Primaria/normas , Adulto , Actitud del Personal de Salud , Estudios Transversales , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/normas , Factores Sexuales , Factores SocioeconómicosRESUMEN
5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20 g were divided into five groups: control, 5-FU (50 mg/kg), 5-FU + MEL (2.5, 5 & 10 mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.
RESUMEN
Introduction: Diabetes is associated with several debilitating complications, including the development of diabetic foot ulcers (DFUs), which can have serious consequences. This study emphasizes a multidisciplinary approach, providing a thorough overview of DFU pathogenesis and available treatments. Methods: An extensive literature review, covering studies published between 2000 and 2023, was conducted to gather data on DFU pathophysiology and treatments, including wound dressings, photobiomodulation, off-loading devices, adjunct medicines, and stem cell therapy. Results: DFUs are complicated due to infection, ischemia, and neuropathy. Sufficient wound dressings maintain a moist environment, promoting autolytic debridement and facilitating the healing process. Through cellular mechanisms, photobiomodulation therapy (PBM) was observed to expedite the healing process. Additionally, off-loading devices were invented to reduce ulcer pressure and promote healing. Adjunct therapies such as negative pressure wound therapy and hyperbaric oxygen therapy were identified as valuable tools for enhancing healing outcomes. Furthermore, autologous and allogeneic stem cell treatments exhibited the potential for promoting tissue regeneration and expediting the healing process. Conclusion: The complex pathophysiology of DFUs necessitates a multimodal treatment approach. Essential components include PBM, wound dressings, off-loading devices, adjunct treatments, and stem cell therapy.
RESUMEN
Background: Schistosoma mansoni infection poses a substantial public health challenge globally, and the World Health Organization (WHO) aims for the elimination of schistosomiasis by 2030. This study aimed to assess the current prevalence of human S. mansoni infection in endemic regions worldwide between 2010 and 2024. Methods: We conducted a comprehensive search in PubMed/Medline and Scopus databases as well as other public sources from 1 January 2010 to 15 July 2024. Population-based studies reporting the prevalence of S. mansoni infection were eligible. We undertook a random-effects meta-analysis to estimate pooled prevalences with 95% confidence intervals (CIs) in WHO-defined regions and assessed potential risk factors associated with S. mansoni infection. The protocol for this study was registered on PROSPERO (CRD42023438455). Findings: We identified a total of 542 eligible studies involving 1,163,866 individuals who had been tested for S. mansoni infection in 38 countries. The overall, pooled global prevalence of S. mansoni infection in endemic region was 14.8% (95% CI, 13.5%-16.1%). The pooled prevalences (95% CI) in specific regions were: 15.3% (13.9-16.8%) in sub-Saharan Africa, 12.4% (8.9-16.4%) in South America and 9.5% (5.4-14.6%) in the Eastern Mediterranean region. There was a 52.6% decrease in prevalence of S. mansoni infection and a 37% decrease in high-intensity infection for studies conducted between 2010 and 2014 compared to those conducted between 2020 and 2023. The present analysis revealed that factors including male gender, bathing or swimming in natural water bodies, crossing rivers or lakes, and engaging in water irrigation activities such as fishing, working in rice paddies or maintaining irrigation canals were significantly associated with S. mansoni infection. Interpretation: The findings of this investigation revealed that, despite a decline in prevalence and high-intensity infection, 7-12% of people in endemic regions, notably in sub-Saharan Africa, remained affected by schistosomiasis mansoni between 2020 and 2024. This study provides data of relevance to policymakers to support efforts to eliminate this disease. Funding: This study received no funding.
RESUMEN
A general method for compressing the modulation time-bandwidth product of analog signals is introduced. As one of its applications, this physics-based signal grooming, performed in the analog domain, allows a conventional digitizer to sample and digitize the analog signal with variable resolution. The net result is that frequency components that were beyond the digitizer bandwidth can now be captured and, at the same time, the total digital data size is reduced. This compression is lossless and is achieved through a feature selective reshaping of the signal's complex field, performed in the analog domain prior to sampling. Our method is inspired by operation of Fovea centralis in the human eye and by anamorphic transformation in visual arts. The proposed transform can also be performed in the digital domain as a data compression algorithm to alleviate the storage and transmission bottlenecks associated with "big data."
Asunto(s)
Algoritmos , Biomimética/métodos , Compresión de Datos/métodos , Fóvea Central/fisiología , Interpretación de Imagen Asistida por Computador/métodos , Modelos Biológicos , Percepción Visual/fisiología , Simulación por Computador , HumanosRESUMEN
Low frequency electrical stimulation has been revealed that as a potential cure in patient with drug resistant to epilepsy. This study tries to evaluate the effect of low frequency electrical stimulation (LFS) on absence seizure of perioral region primary somatosensory cortex (S1po). Eighteen male WAG/Rij rats were received LFS (3Hz, square wave, monophasic, 200µs, and 400µA) for 25min into S1po for a period of five days. There is 6 animals per group .The stimulating electrodes were implanted according to stereotaxic landmarks and EEG recording was obtained 30min before and after LFS to analyse frequency, number and duration of spike-wave discharges (SWD). The results showed that in animals with unilateral stimulating electrodes (Exp1) in first and second days and also in animals with bilateral stimulating electrodes (Exp2) in days 3rd and 4th. LFS had significant decrease effects (p<0.05) on mean number of SWD between pre-LFS. In comparison pre-LFS to post-LFS, mean of duration in Exp2 decreased significantly. In continuous application of LFS (5 days) only the data of first day was differently significant (p<0.05) but data of other days had no difference. Comparison of data between Exp1, Exp2 and control groups showed that the mean number of Exp1 was significantly different (p<0.05) and mean pick frequency in Exp2 was significantly decreased in comparison with Exp1 group (p<0.05). The LFS of S1po produces significant antiepileptic effect on absence seizure but it was not persistent till the next day and shows a short time effect.