161 research outputs found
Overexpression of SPARC obliterates the in vivo tumorigenicity of human hepatocellular carcinoma cells
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide. Current treatments are extremely disappointing. SPARC (Secreted protein, acidic and rich in cysteine) is a matricellular glycoprotein with differential expression in several tumors, including HCC, which significance remains unclear. We infected HCC cells (HepG2, Hep3B and Huh7) with an adenovirus expressing SPARC (AdsSPARC) to examine the role of SPARC expression on HCC cells and its effect on tumor aggressiveness. The in vitro HCC cells substrate-dependent proliferation and cell cycle profile were unaffected; however, SPARC overexpression reduced HCC proliferation when cells were grown in spheroids. A mild induction of cellular apoptosis was observed upon SPARC overexpression. SPARC overexpression resulted in spheroid growth inhibition in vitro while no effects were found when recombinant SPARC was exogenously applied. Moreover, the clonogenic and migratory capabilities were largely decreased in SPARC-overexpressing HCC cells, altogether suggesting a less aggressive HCC cell phenotype. Consistently, AdsSPARC-transduced cells showed increased E-cadherin expression and a concomitant decrease in N-cadherin expression. Furthermore, SPARC overexpression was found to reduce HCC cell viability in response to 5-FU-based chemotherapy in vitro, partially through induction of apoptosis. In vivo experiments revealed that SPARC overexpression in HCC cells inhibited their tumorigenic capacity and increased animal survival through a mechanism that partially involves host macrophages. Our data suggest that SPARC overexpression in HCC cells results in a reduced tumorigenicity partially through the induction of mesenchymal-to-epithelial transition (MET). These evidences point to SPARC as a novel target for HCC treatment.Fil: Atorrasagasti, MarĂa Catalina. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Laboratorio de Terapia GenĂ©tica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Malvicini, Mariana. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Laboratorio de Terapia GenĂ©tica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Aquino, Jorge Benjamin. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Laboratorio de Terapia GenĂ©tica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Alaniz, Laura Daniela. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Laboratorio de Terapia GenĂ©tica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: GarcĂa, Mariana Gabriela. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Laboratorio de Terapia GenĂ©tica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Rizzo, Manglio Miguel. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Laboratorio de Terapia GenĂ©tica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Laboratorio de Terapia GenĂ©tica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
Dual effect of Thymosin α 1 on human monocyte-derived dendritic cellin vitrostimulated with viral and bacterial toll-like receptor agonists
OBJECTIVES:
Thymosin α 1 (Tα1) recently gained interest as immune adjuvant for vaccines because of its ability to modulate the T-cell/dendritic cell (DC) axis and to improve antibody production. The objective of this study was to determine whether Tα1 would address in vitro the response of human primary monocyte-derived DC, crucial regulators of vaccine-induced immunity, upon exposure to different toll-like receptor (TLR) agonists or infection with viruses or bacteria.
METHODS:
DC maturation and production of pro-inflammatory cytokines were analyzed.
RESULTS:
Our data revealed a dual effect of Tα1 on DC biology upon viral or bacterial stimulation. Interestingly, Tα1 enhanced human leukocyte antigen (HLA)-I and II surface expression and secretion of IL-6, TNF-α and IL-8 when DCs were treated with viral TLR3 and TLR7/8 agonists. Similarly, in pandemic H1N1 influenza A-infected DCs, Tα1 raised the expression of maturation markers and type I and III Interferon (IFN). In contrast, following bacterial TLR2 and 4 stimulation, as well as upon Bacillus Calmette-Guerin infection, the presence of Tα1 in DC cultures drastically lowered the analyzed cellular parameters.
CONCLUSION:
The knowledge that Tα1 pleiotropic effect might ameliorate anti-viral immune responses and, at the same time, dampen inflammation caused by bacterial infections could lay the groundwork for a more appropriate therapeutic application of this molecule
Tumor associated fibroblast: impact on osteosarcoma primary and metastatic tumoral microenvironment and treatment response
Tumor associated fibroblast (TAF) have been implicated in almost every aspect of tumoral biology. Of relevance TAF could be modulating response to treatment and overall microenvironment development. Given that Osteosarcoma (OS) have the same 5-year survival rate for metastatic and treatment resistant patients since 1970 Ìs, we dediced to investigate the role of TAF in OS primary and metastatic niches. Aim: Evaluate TAF and human OS cell lines interaction in primary and pulmonary metastatic environments. To analyze if metastatic OS cell line has a higher inducing power than non-metastatic OS cell line analyzing the expression of different ABC transporters im-plicated in chemoresistance and the ability to exclude doxorubicin and rhodamine. Methods: The expression of ABC transporters was analyzed by RT-qPCR on conditioned fibroblast. Rhodamine 123 exclution assay was used to determine the activity of P-glycoprotein (P-gp) mediated transport and doxorubicin (DOX) exclution was performed to analysis the overall ABC-related chemoresistant capacity. To evaluate the interaction of fibroblast with metastatic (LM7) and non-metastatic (SAOS2) OS human cells hetero â spheroid formation assays were performed. Results: LM7 conditioned medium (CM) induced an overall upregulation of ABC transporters in comparison with SAOS2 CM. Conditioned fibroblast with LM7 CM showed lower levels of intracellular DOX and Rhodomine in comparison with SAOS2 CM fibroblast. Mixed spheroid compose of fibroblast ans OS cell lines display a lower area and more compact than single type aggregates. OS has not changed the 5-year rate survival for metastatic patients since the 70â, so the need to understand aspects of OS metastatic biology and chemoresistance could be helpful to develop new treat-ments to this group. Knowing aspects of the associated stroma and in particular TAF, could allow the development of new therapeutic possibilities targeting the tumoral associated stroma.Fil: Valenzuela Alvarez, Matias Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Rizzo, Matias Eduardo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Auzmendi, Jeronimo. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Lazarowski, Alberto. Universidad de Buenos Aires; ArgentinaFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaLXVI ReuniĂłn Anual de la Sociedad Argentina de InvestigaciĂłn ClĂnica: LXIX ReuniĂłn Anual de la Sociedad Argentina de InmunologĂa; LIII ReuniĂłn Anual de la AsociaciĂłn Argentina de FarmacologĂa Experimental y XI ReuniĂłn Anual de la AsociaciĂłn Argentina de NanomedicinasArgentinaSociedad Argentina de InvestigaciĂłn ClĂnicaSociedad Argentina de InmunologĂaAsociaciĂłn Argentina de FarmacologĂa Experimenta
Impact of two different exercise programs on persistent cancer-related fatigue and physical fitness
Cancer-related fatigue is a common symptom in patients with cancer, which is experienced by 70% to 100% of these patients and brings some impairment of physical and mental performance, hinders their working or carrying out regular daily activities, and hence results in a substantial reduction of the quality of life. Physical exercise has consistently been identified as a central element of rehabilitation for many chronic diseases like cancer, and increasing evidence supports the contention that physical activity is a valuable intervention that can be utilized in conjunction with conventional therapies during CRF treatment. Objective: The aim of this study was to assess the impact of a program of physical exercise on fatigue levels and physical performance of cancer patients. Method: A consecutive series of 44 adult patients with neoplastic disease (solid or hematological), with a medical diagnosis of fatigue, who were enrolled in an oncological treatment, with the ability to walk and willing to enter a rehabilitation program of exercise for at least 4 consecutive months. The exercise program was performed two times per week, each session lasting one hour and consisting of aerobic, resistance, and flexibility exercises. The protocol was divided into aerobic exercise and resistance training combined with aerobic exercise. The patients were evaluated with two assessments: one prior to their beginning the exercise program and other at the end of the four-month program. In both assessments the patients completed the Revised Piper Fatigue Scale and the six-minute walk test. The primary outcome of change over baseline and after 16 weeks in PFS-R score and six-minute walk test were compared using a two sample two-sided t-test for both groups. Alpha level was set at p < 0.05. Results: After 16 weeks, the patients who participated in the aerobic or the combined exercise program reported significantly higher levels of physical functioning (6-minute walking test, p = 0.0009 and p = 0.001, respectively) and significantly lower fatigue (PFS-R, p = 0.003 and p = 0.002, respectively) than at the beginning the exercise program. Conclusion: The results of patients who underwent aerobic or aerobic + anaerobic exercise showed statistically significant improvement of physical performance and of fatigue. Data from this study corroborates with the literature showing that exercise programs with aerobic or resistance exercises are an effective strategy for the treatment of fatigue. The results of this study confirm that physical exercise could be useful in rehabilitation of cancer survivors, especially for fatigued patients.A fadiga relacionada ao cĂąncer Ă© um dos sintomas mais comuns entre pacientes com cĂąncer, relatada em 70% a 100% desses pacientes resultando em uma reduçao significativa da qualidade de vida, funcionalidade e independĂȘncia. O exercĂcio fĂsico tem sido identificado como um elemento central de reabilitaçao de muitas doenças crĂŽnicas como cĂąncer, e cada vez mais evidĂȘncias apoiam a tese de que a atividade fĂsica Ă© uma intervençao Ăștil, que pode ser utilizada em conjunto com terapias convencionais durante o tratamento da fadiga relacionada ao cĂąncer. Objetivo: Avaliar o impacto de dois programas de exercĂcio fĂsico sobre os nĂveis de fadiga e desempenho fĂsico de pacientes com cĂąncer. MĂ©todo: Relato de uma sĂ©rie consecutiva de 44 doentes adultos com doença neoplĂĄsica (sĂłlido ou hematolĂłgicas), e diagnĂłstico mĂ©dico de fadiga, submetidos a dois diferentes programas de exercĂcio fĂsico. Todos os doentes foram avaliados quanto a desempenho fĂsico com o uso do teste de caminhada de 6 minutos e avaliados quanto aos nĂveis de fadiga com o teste de Piper, antes e depois de 4 meses de atividade fĂsica supervisionada (exercĂcios aerĂłbicos isolados e treino de resistĂȘncia combinado ao exercĂcios aerĂłbicos). Resultados: ApĂłs 16 semanas, os doentes que participaram do programa de exercĂcios aerĂłbicos ou que participaram do protocolo de exercĂcio aerĂłbico combinado com anaerĂłbio, relataram nĂveis significativamente mais elevados do desempenho fĂsico (6 minutos teste de caminhada, p = 0,0009 e p = 0,001, respectivamente) e nĂveis de fadiga significativamente menor (PFS- R, p = 0,003 e p = 0,002, respectivamente) do que no inĂcio do programa de exercĂcios. ConclusĂŁo: Estes resultados demonstram que tanto um protocolo de exercĂcio aerĂłbico quanto de exercĂcio aerĂłbico combinado com exercĂcio anaerĂłbio apresentam melhora significativa do desempenho fĂsico e dos nĂveis de fadiga de doentes oncolĂłgicos. Os dados deste estudo corroboram a literatura mostrando que a atividade fĂsica Ă© uma estratĂ©gia eficaz para o tratamento da fadiga. Os resultados deste estudo confirmam que o exercĂcio fĂsico pode ser Ăștil na reabilitaçao de sobreviventes de cĂąncer, especialmente para pacientes com fadiga oncolĂłgica
Composting process evaluation of two mixtures of poultry manures
Los residuos del sector avĂcola,
principalmente guano (aves ponedoras) y
cama de parrilleros (aves de engorde), pueden
generar un impacto negativo en el ambiente
contribuyendo a la contaminaciĂłn de suelo,
agua y aire. La estabilización aeróbica a través
del compostaje es una alternativa de tratamiento
para reducir la contaminaciĂłn. El objetivo de este
trabajo fue evaluar el proceso de compostaje en
dos mezclas con diferentes porcentajes de residuos
avĂcolas (guano de aves ponedoras y cama de
pollos parrilleros). Se compostaron dos mezclas
que contenĂan 81% y 70% de residuos avĂcolas
durante 16 semanas. Las variables analizadas
fueron: temperatura (T°), pH, conductividad
eléctrica (CE), humedad (H), capacidad de
intercambio catiĂłnico (CIC), carbono orgĂĄnico
total (COT), amonio (NH4+), nitrato (NO3
- ), nitrĂłgeno total (NT ) y carbono soluble (CS). Las caracterĂsticas
finales de los compost A y B fueron: pH 7,1 - 6,8,
CE 3,3 - 2,9 (mS. cm- 1), COT 14,8 - 17,9 %, NT
0,97 - 0,88 %, NH4 + 501 - 144,9 mg kg-1, NO3-552,3 - 543,0 mg kg-1 respectivamente. El proceso de compostaje podrĂa ser una herramienta para
estabilizar los residuos avĂcolas minimizando su impacto en el ambiente.Chicken production wastes, principally
poultry manure (layers) and litter
(from chickens for fattening), may impact
negatively on the environment, contributing to
soil, water and air pollution. Aerobic stabilization
through composting is an alternative to reduce
contamination. This study aims to evaluate
the composting process in two mixtures with
different percentages of poultry manure of
laying chickens and broiler poultry litter.
Two mixtures were composted containing 81%
and 70% of poultry wastes for 16 weeks. The
analytical parameters were: temperature (T°),
pH, electrical conductivity (EC), humidity (H),
cationic exchange capacity (CEC), total
organic carbon (TOC), amonium (NH4+),
nitrate (NO3- ), total nitrogen (TN), soluble
carbon soluble (SC) were determined in
each treatment. The final compost A and
B characteristics were 7,1 - 6,8, CE 3,3 -
2,9 (mS.cm-1), COT 14,8 - 17,9%, NT 0.97 -
0.88%, NH4+ 501 - 144,9 mg kg-1, NO3
- 552,3 -543,0 mg kg-1 respectively. The composting
process may be a tool to stabilize poultry
wastes, minimizing its environmental damage.Fil: Riera, NicolĂĄs I..
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola.Fil: Della Torre, Virginia.
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola.Fil: Rizzo, Pedro F..
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola.Fil: Butti, Mariano.
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola.Fil: Bressan, Fabiana M..
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola.Fil: Zarate, Natalia.
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola.Fil: Weigandt, Cristian.
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola.Fil: Crespo, Diana Elvira.
Instituto Nacional de TecnologĂa Agropecuaria Castelar (Buenos Aires). Laboratorio de TransformaciĂłn de Residuos, Instituto de MicrobiologĂa y ZoologĂa AgrĂcola
Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic hepatitis C virus infection
CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation (CIA). Here, we found that both apoptotic epitope (AE)-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper-1-like signature program in chronic (c)HCV infection. However, AE-specific CD8(+) T cells produced tumor necrosis factor (TNF)-α and interleukin-2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations acquiring high levels of programmed death-1 receptor expression. Contextually, only AE-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Taken together, these data suggest that AE-specific CD8(+) T cells can sustain CIA by their capacity to produce TNF-α and be resistant to inhibitory signals more than HCV-specific CD8(+) T cells in cHCV infection
Attitudes, knowledge and Practices of Nurses towards HIV/AIDS Patients. An Observational, Cross Sectional, Multicenter study
Background. Attitudes, knowledge and practices of nurses towards HIV/AIDS patients are of continuous interest, especially in developing countries. However, in Italy, this topic is still scarcely debated. Materials and methods. An observational, cross sectional, multicentre study was conducted on a sample of 144 nurses in two Italian Hospitals of the Puglia Region ("Vito Fazzi" Hospital in Lecce and "San Giuseppe da Copertino" Hospital in Copertino (Le)). Results. A large part of the sample (97.2%, n=140) stated that they never refused to take care of a patient with AIDS. Only 22.9%, (n=33), of the sample had attended a training course and almost half (63.2%, n=91) used the gloves regularly when performing blood samples or when administering therapy to patients. With regard to the assessment of HIV knowledge, the percentage of nurses who know the meaning of the terms " seropositive" (83.3%, n=120), "HIV-positive person" (91.7%, n=132) and "window period" (47.9%, n=69) decreased. Conclusions. The results of the study show that a non-negligible percentage of nurses could be considered at risk of infection due to non-routine use of gloves, incorrect handling of the patient's biological samples and not knowing how to decontaminate a surface with potentially infected blood
Impact of Mycobacterium tuberculosis RD1-locus on human primary dendritic cell immune functions
Modern strategies to develop vaccines against Mycobacterium tuberculosis (Mtb) aim to improve the current Bacillus Calmette-Guerin (BCG) vaccine or to attenuate the virulence of Mtb vaccine candidates. In the present study, the impact of wild type or mutated region of difference 1 (RD1) variants on the immunogenicity of Mtb and BCG recombinants was investigated in human primary dendritic cells (DC). A comparative analysis of transcriptome, signalling pathway activation, maturation, apoptosis, cytokine production and capacity to promote Th1 responses demonstrated that DC sense quantitative and qualitative differences in the expression of RD1-encoded factors - ESAT6 and CFP10 - within BCG or Mtb backgrounds. Expansion of IFN-Îł producing T cells was promoted by BCG::RD1-challenged DC, as compared to their BCG-infected counterparts. Although Mtb recombinants acted as a strong Th-1 promoting stimulus, even with RD1 deletion, the attenuated Mtb strain carrying a C-terminus truncated ESAT-6 elicited a robust Th1 promoting phenotype in DC. Collectively, these studies indicate a necessary but not sufficient role for the RD1 locus in promoting DC immune-regulatory functions. Additional mycobacterial factors are likely required to endow DC with a high Th1 polarizing capacity, a desirable attribute for a successful control of Mtb infection
Role of cannabinoids in the treatment of Tinnitus
Tinnitus is a frequent symptom in audiological clinical practice characterized by an abnormal noise perceived in one or both ears or in the head, in which a patient has a conscious hearing percept in absence of external sound. Tinnitus might be caused by a homeostatic response of central dorsal cochlear nucleus auditory neurons that makes them hyperactive in compensation to auditory input loss. One hypothesis suggests that tinnitus is a sensory form of epilepsy that involves the cochlear nucleus and the inferior colliculus, which display impairment in the electrical activity in the auditory system. This alteration determines a synaptic plasticity in the dorsal cochlear nucleus that becomes a target for pharmacological compounds able to treat tinnitus. There is no effective drug treatment for tinnitus, but different studies propose the use of cannabinoid receptors agonist for their anti-epileptic activity, although their practical effects are still unclear. In this review, we want to analyze the emerging pharmacological approaches of cannabinoid receptor agonists to the therapy of tinnitus
V-Edge: Virtual Edge Computing as an Enabler for Novel Microservices and Cooperative Computing
As we move from 5G to 6G, edge computing is one of the concepts that needs
revisiting. Its core idea is still intriguing: instead of sending all data and
tasks from an end user's device to the cloud, possibly covering thousands of
kilometers and introducing delays that are just owed to limited propagation
speed, edge servers deployed in close proximity to the user, e.g., at some 5G
gNB, serve as proxy for the cloud. Yet this promising idea is hampered by the
limited availability of such edge servers. In this paper, we discuss a way
forward, namely the virtual edge computing (V-Edge) concept. V-Edge bridges the
gap between cloud, edge, and fog by virtualizing all available resources
including the end users' devices and making these resources widely available
using well-defined interfaces. V-Edge also acts as an enabler for novel
microservices as well as cooperative computing solutions. We introduce the
general V-Edge architecture and we characterize some of the key research
challenges to overcome, in order to enable wide-spread and even more powerful
edge services
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