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1.
Inflamm Res ; 70(2): 229-239, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33404674

RESUMO

OBJECTIVE: One of the main challenges in liver cell therapy is the replacement of damaged cells and the induction of a tolerogenic microenvironment to promote graft acceptance by the recipient. Adult-derived human liver stem/progenitor cells (ADHLSCs) are currently evaluated at the clinical levels as a promising pro-regenerative and immune-modulatory tool. The expression profile of several immunological molecules may influence the local immune-inflammatory response and, therefore, modulate the tissue healing process. To increase the quality and safety of ADHLSCs before transplantation requires an appropriate analysis and characterization of their pattern expression of immune-inflammatory-associated molecules. METHODS: The expression of 27 molecules belonging to T-cell co-stimulatory pathway, CD47 partners, Ikaros family, CD300 family and TNF family were analyzed using flow cytometry. We compared their expression profiles to PBMCs, hepatocytes and ADHLSCs in both expansion and after hepatogenic differentiation culture conditions. RESULTS: This original immuno-comparative screening revealed that liver cell populations do not constitutively present significant immunological pattern compared to PBMCs. Moreover, our findings highlight that neither the expansion nor the hepatogenic differentiation induces the expression of immune-inflammatory molecules. The detailed expression characteristics (percentage of positive cells and median fluorescence intensity) of each molecule were analyzed and presented. CONCLUSION: By analyzing 27 relevant molecules, our immuno-comparative screening demonstrates that ADHLSCs keep a non-immunogenic profile independent of their expansion or hepatogenic differentiation state. Accordingly, the immunological profile of ADHLSCs seems to support their safe and efficient use in liver tissue therapeutic repair strategy.


Assuntos
Fígado/citologia , Células-Tronco/imunologia , Adulto , Antígenos CD/imunologia , Diferenciação Celular , Células Cultivadas , Hepatócitos/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Transplante de Células-Tronco , Linfócitos T/imunologia
2.
J Cell Physiol ; 234(11): 21145-21152, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31041809

RESUMO

Adipose tissue-derived mesenchymal stromal cells (ASCs) hold the promise of achieving successful immunotherapeutic results due to their ability to regulate different T-cell fate. ASCs also show significant adaptability to environmental stresses by modulating their immunologic profile. Cell-based therapy for inflammatory diseases requires a detailed understanding of the molecular relation between ASCs and Th17 lymphocytes taking into account the influence of inflammation and cell ratio on such interaction. Accordingly, a dose-dependent increase in Th17 generation was only observed in high MSC:T-cell ratio with no significant impact of inflammatory priming. IL-23 receptor (IL-23R) expression by T cells was not modulated by ASCs when compared to levels in activated T cells, while ROR-γt expression was significantly increased reaching a maximum in high (1:5) unprimed ASC:T-cell ratio. Finally, multiplex immunoassay showed substantial changes in the secretory profile of 15 cytokines involved in the Th17 immune response (IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40, and TNF-α), which was modulated by both cell ratio and inflammatory priming. These findings suggest that Th17 lymphocyte pathway is significantly modulated by ASCs that may lead to immunological changes. Therefore, future ASC-based immunotherapy should take into account the complex and detailed molecular interactions that depend on several factors including inflammatory priming and cell ratio.


Assuntos
Células-Tronco Mesenquimais/imunologia , Células Th17/imunologia , Diferenciação Celular/imunologia , Humanos , Ativação Linfocitária/imunologia
3.
Inflamm Res ; 68(3): 203-213, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30506263

RESUMO

OBJECTIVE AND DESIGN: The objective of the study is to uncover the influence of human bone marrow-derived mesenchymal stem cells (BM-MSCs) on the generation of Th17 lymphocytes in co-cultures of both BM-MSCs and T cells. MATERIALS AND METHODS: BM-MSCs, characterized according to the international society for cellular therapy (ISCT) criteria, were co-cultured with T cells isolated from peripheral blood. The expression levels of IL-17 receptor, RORγt and IL-23 receptor were evaluated using flow cytometry. The levels of cytokines involved in Th17 immunomodulation were measured using multiplex assay. TREATMENT: Inflammatory primed and non-primed BM-MSCs were co-cultured with either activated or non-activated T cells either at (1/80) and (1/5) ratio respectively. RESULTS: MSC/T-cell ratio and inflammation significantly influenced the effect of BM-MSCs on the generation of Th17 lymphocytes. Cocultures of either primed or non-primed BM-MSCs with activated T cells significantly induced IL-17A-expressing lymphocytes. Interestingly, the expression of the transcription factor RORγt was significantly increased when compared to levels in activated T cells. Finally, both cell ratio and priming of BM-MSCs with cytokines substantially influenced the cytokine profile of BM-MSCs and T cells. CONCLUSION: Our findings suggest that BM-MSCs significantly modulate the Th17 lymphocyte pathway in a complex manner.


Assuntos
Células-Tronco Mesenquimais/imunologia , Células Th17/imunologia , Células da Medula Óssea/citologia , Técnicas de Cocultura , Citocinas/imunologia , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Receptores de Interleucina/imunologia
4.
Pastoral Psychol ; 66(4): 461-485, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28725087

RESUMO

Pastoral psychologists have long tried to establish a working model that encompasses the seemingly conflicting disciplines of science and religion. Psychosynthesis, a transpersonal psychology and therapeutic approach, offers such a model of the human personality, in which the psychological and spiritual perspectives can converge. This article explores psychosynthesis psychology and therapy as a theoretical framework for pastoral psychology. Although psychosynthesis psychotherapy relies on an array of techniques, it fundamentally works with the clients' will while emphasizing, exploring, and cultivating their relationships on all levels-intrapersonal, interpersonal, and with the Higher Self. In addition to the subconscious, psychosynthesis includes a higher psychological plane, called the superconscious, from which our higher ethical, aesthetic, scientific, and spiritual values are derived. This article begins by introducing psychosynthesis concepts and techniques. It then provides qualitative findings showing that psychosynthesis counseling helped to awaken spirituality in three out of eleven clients who had formerly identified themselves as atheists. In addition, testimonies are included that show that psychosynthesis counseling also helped all eleven clients to attain personal growth. Finally, the counselor describes her experience of psychosynthesis as a Christian in the therapeutic setting. The framework of psychosynthesis psychology and its techniques are viable methodologies for anyone searching to incorporate spiritual growth into a psychological working model.

5.
PLoS Med ; 13(1): e1001941, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26785406

RESUMO

BACKGROUND: Obesity is reaching epidemic proportions in both developed and developing countries. Even modest weight gain increases the risk for chronic illness, yet evidence-based interventions to prevent weight gain are rare. This trial will determine if a simple low-intensity intervention can prevent weight gain in women compared to general health information. METHODS AND FINDINGS: We conducted a 1-yr pragmatic, cluster randomised controlled trial in 41 Australian towns (clusters) randomised using a computer-generated randomisation list for intervention (n = 21) or control (n = 20). Women aged 18 to 50 yr were recruited from the general population to receive a 1-yr self-management lifestyle intervention (HeLP-her) consisting of one group session, monthly SMS text messages, one phone coaching session, and a program manual, or to a control group receiving one general women's health education session. From October 2012 to April 2014 we studied 649 women, mean age 39.6 yr (+/- SD 6.7) and BMI of 28.8 kg/m(2) (+/- SD 6.9) with the primary outcome weight change between groups at 1 yr. The mean change in the control was +0.44 kg (95% CI -0.09 to 0.97) and in the intervention group -0.48 kg (95% CI -0.99 to 0.03) with an unadjusted between group difference of -0.92 kg (95% CI -1.67 to -0.16) or -0.87 kg (95% CI -1.62 to -0.13) adjusted for baseline values and clustering. Secondary outcomes included improved diet quality and greater self-management behaviours. The intervention appeared to be equally efficacious across all age, BMI, income, and education subgroups. Loss to follow-up included 23.8% in the intervention group and 21.8% in the control group and was within the anticipated range. Limitations include lack of sensitive tools to measure the small changes to energy intake and physical activity. Those who gained weight may have been less inclined to return for 1 yr weight measures. CONCLUSIONS: A low intensity lifestyle program can prevent the persistent weight gain observed in women. Key features included community integration, nonprescriptive simple health messages, small changes to behaviour, low participant burden, self-weighing, and delivery including a mix of group, phone, and SMS text reminders. The findings support population strategies to halt the rise in obesity prevalence.


Assuntos
Comportamentos Relacionados com a Saúde , Obesidade/prevenção & controle , Comportamento de Redução do Risco , População Rural , Aumento de Peso/fisiologia , Adulto , Peso Corporal/fisiologia , Análise por Conglomerados , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/epidemiologia , Vitória/epidemiologia
7.
Int J Behav Nutr Phys Act ; 11: 134, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25358909

RESUMO

BACKGROUND: Pregnancy is a recognised high risk period for excessive weight gain, contributing to postpartum weight retention and obesity development long-term. We aimed to reduce postpartum weight retention following a low-intensity, self-management intervention integrated with routine antenatal care during pregnancy. METHODS: 228 women at increased risk of gestational diabetes, <15 weeks gestation were randomised to intervention (4 self-management sessions) or control (generic health information). Outcomes, collected at baseline and 6 weeks postpartum, included anthropometrics (weight and height), physical activity (pedometer) and questionnaires (health behaviours). RESULTS: Mean age (32.3 ± 4.7 and 31.7 ± 4.4 years) and body mass index (30.4 ± 5.6 and 30.3 ± 5.9 kg/m2) were similar between intervention and control groups, respectively at baseline. By 6 weeks postpartum, weight change in the control group was significantly higher than the intervention group with a between group difference of 1.45 ± 5.1 kg (95% CI: -2.86,-0.02; p < 0.05) overall, with a greater difference in weight found in overweight, but not obese women. Intervention group allocation, higher baseline BMI, GDM diagnosis, country of birth and higher age were all independent predictors of lower weight retention at 6 weeks postpartum on multivariable linear regression. Other factors related to weight including physical activity, did not differ between groups. CONCLUSIONS: A low intensity intervention, integrated with standard antenatal care is effective in limiting postpartum weight retention. Implementation research is now required for scale-up to optimise antenatal health care. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry Number: ACTRN12608000233325. Registered 7/5/2008.


Assuntos
Comportamentos Relacionados com a Saúde , Período Pós-Parto , Aumento de Peso , Adulto , Índice de Massa Corporal , Diabetes Gestacional , Dieta , Feminino , Humanos , Estilo de Vida , Atividade Motora , Obesidade/prevenção & controle , Sobrepeso/prevenção & controle , Gravidez , Cuidado Pré-Natal , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento
8.
BMC Public Health ; 14: 608, 2014 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-24930478

RESUMO

BACKGROUND: To impact on the obesity epidemic, interventions that prevent weight gain across populations are urgently needed. However, even the most efficacious interventions will have little impact on obesity prevention unless they are successfully implemented in diverse populations and settings. Implementation research takes isolated efficacy studies into practice and policy and is particularly important in obesity prevention where there is an urgent need to accelerate the evidence to practice cycle. Despite the recognised need, few obesity prevention interventions have been implemented in real life settings and to our knowledge rarely target rural communities. METHODS: Here we describe the rationale, design and implementation of a Healthy Lifestyle Program for women living in small rural communities (HeLP-her Rural). The primary goal of HeLP-her Rural is to prevent weight gain using a low intensity, self-management intervention. Six hundred women from 42 small rural communities in Australia will be randomised as clusters (n-21 control towns and n = 21 intervention towns). A pragmatic randomised controlled trial methodology will test efficacy and a comprehensive mixed methods community evaluation and cost analysis will inform effectiveness and implementation of this novel prevention program. DISCUSSION: Implementing population interventions to prevent obesity is complex, costly and challenging. To address these barriers, evidence based interventions need to move beyond isolated efficacy trials and report outcomes related to effectiveness and implementation. Large pragmatic trials provide an opportunity to inform both effectiveness and implementation leading to potential for greater impact at the population level. Pragmatic trials should incorporate both effectiveness and implementation outcomes and a multidimensional methodology to inform scale-up to population level. The learnings from this trial will impact on the design and implementation of population obesity prevention strategies nationally and internationally. TRIAL REGISTRATION: ANZ clinical trial registry ACTRN12612000115831. Date of registration 24/01/2012.


Assuntos
Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Obesidade/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/prevenção & controle , Desenvolvimento de Programas , Projetos de Pesquisa , População Rural , Vitória/epidemiologia , Saúde da Mulher
9.
Aust N Z J Obstet Gynaecol ; 54(4): 382-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24738837

RESUMO

Self-weighing is important for weight management in general populations; however its role in optimising gestational weight gain is less clear. Our randomised trial in early pregnancy found regular self-weighing when combined with a self-management intervention, optimised weight gain at 28 weeks gestation (5.66 ± 2.6 kg vs 7.03 ± 3.56 kg, P = 0.02) and reduced postpartum weight retention (-0.57 ± 3.94 kg vs 1.48 ± 5.49 kg, P < 0.05) compared with control participants. Results highlight the importance of self-monitoring strategies during pregnancy.


Assuntos
Estilo de Vida , Autocuidado , Aumento de Peso , Redução de Peso , Adulto , Terapia Comportamental , Feminino , Humanos , Obesidade/terapia , Cuidado Pós-Natal , Gravidez , Cuidado Pré-Natal , Programas de Redução de Peso
10.
Cells ; 13(2)2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38247860

RESUMO

As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs.


Assuntos
Interleucina-17 , Células-Tronco Mesenquimais , Células Th17 , Técnicas de Cocultura , Imunomodulação
11.
Vaccines (Basel) ; 10(10)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36298457

RESUMO

(1) Background: The Vaccine Coverage Rate of influenza remains low and omnichannel efforts are required to improve it. The objective was to evaluate the feasibility and outcomes of a QR Code nudging system in outpatient departments. (2) Methods: The study was performed in 6 departments ensuring ambulatory activities in a French university Hospital between November and December 2021. By scanning QR codes, users accessed anonymously to the ELEFIGHT® web app, which provides medical information on influenza and invites them to initiate a discussion about influenza prevention with their physicians during the consultation. (3) Results: 351 people made 529 scans with an average reading time of 1 min and 4 s and a conversion rate of 32%, i.e., people willing to engage in a discussion. (4) Conclusions: The study suggests that direct access to medical information through QR codes in hospitals might help nudge people to raise their awareness and trigger their action on influenza prevention.

12.
J Pharmacol Exp Ther ; 339(2): 607-17, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21831965

RESUMO

Marijuana abuse is very prominent among pregnant women. Although marijuana cannabinoids have been shown to exert immunosuppression in adults, virtually nothing is known about the effects of marijuana use during pregnancy on the developing immune system of the fetus and during postnatal life. We noted that murine fetal thymus expressed high levels of the cannabinoid receptors CB1 and CB2. Moreover, perinatal exposure to Δ(9)-tetrahydrocannabinol (THC) had a profound effect on the fetus as evidenced by a decrease in thymic cellularity on gestational days 16, 17, and 18 and postgestational day 1 and marked alterations in T cell subpopulations. These outcomes were reversed by CB1/CB2 antagonists, suggesting that THC-mediated these effects through cannabinoid receptors. Thymic atrophy induced in the fetus correlated with caspase-dependent apoptosis in thymocytes. Thymic atrophy was the result of direct action of THC and not based on maternal factors inasmuch as THC was able to induce T cell apoptosis in vitro in fetal thymic organ cultures. It is noteworthy that perinatal exposure to THC also had a profound effect on the immune response during postnatal life. Peripheral T cells from such mice showed decreased proliferative response to T cell mitogen as well as both T cell and antibody response to HIV-1 p17/p24/gp120 antigens. Together, our data demonstrate for the first time that perinatal exposure to THC triggers profound T cell dysfunction, thereby suggesting that the offspring of marijuana abusers who have been exposed to THC in utero may be at a higher risk of exhibiting immune dysfunction and contracting infectious diseases including HIV.


Assuntos
Dronabinol/efeitos adversos , Feto/imunologia , Antígenos HIV/imunologia , Fumar Maconha/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Psicotrópicos/efeitos adversos , Linfócitos T/imunologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Agonistas de Receptores de Canabinoides , Antagonistas de Receptores de Canabinoides , Caspases/metabolismo , Dronabinol/farmacologia , Feminino , Feto/efeitos dos fármacos , Anticorpos Anti-HIV/biossíntese , HIV-1/imunologia , Indóis/imunologia , Indóis/farmacologia , Ativação Linfocitária , Linfopoese/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Piperidinas/imunologia , Piperidinas/farmacologia , Gravidez , Psicotrópicos/farmacologia , Pirazóis/imunologia , Pirazóis/farmacologia , Receptores de Canabinoides/genética , Receptores de Canabinoides/metabolismo , Rimonabanto , Linfócitos T/efeitos dos fármacos , Timócitos/citologia , Timócitos/imunologia , Timo/embriologia
13.
Int J Behav Nutr Phys Act ; 8: 19, 2011 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-21418609

RESUMO

BACKGROUND: Currently, little is known about physical activity patterns in pregnancy with prior estimates predominantly based on subjective assessment measures that are prone to error. Given the increasing obesity rates and the importance of physical activity in pregnancy, we evaluated the relationship and agreement between subjective and objective physical activity assessment tools to inform researchers and clinicians on optimal assessment of physical activity in pregnancy. METHODS: 48 pregnant women between 26-28 weeks gestation were recruited. The Yamax pedometer and Actigraph accelerometer were worn for 5-7 days under free living conditions and thereafter the International Physical Activity Questionnaire (IPAQ) was completed. IPAQ and pedometer estimates of activity were compared to the more robust and accurate accelerometer data. RESULTS: Of 48 women recruited, 30 women completed the study (mean age: 33.6 ± 4.7 years; mean BMI: 31.2 ± 5.1 kg/m(2)) and 18 were excluded (failure to wear [n = 8] and incomplete data [n = 10]). The accelerometer and pedometer correlated significantly on estimation of daily steps (ρ = 0.69, p < 0.01) and had good absolute agreement with low systematic error (mean difference: 505 ± 1498 steps/day). Accelerometer and IPAQ estimates of total, light and moderate Metabolic Equivalent minutes/day (MET min(-1) day(-1)) were not significantly correlated and there was poor absolute agreement. Relative to the accelerometer, the IPAQ under predicted daily total METs (105.76 ± 259.13 min(-1) day(-1)) and light METs (255.55 ± 128.41 min(-1) day(-1)) and over predicted moderate METs (-112.25 ± 166.41 min(-1) day(-1)). CONCLUSION: Compared with the accelerometer, the pedometer appears to provide a reliable estimate of physical activity in pregnancy, whereas the subjective IPAQ measure performed less accurately in this setting. Future research measuring activity in pregnancy should optimally encompass objective measures of physical activity. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry Number: ACTRN12608000233325. Registered 7/5/2008.


Assuntos
Actigrafia/métodos , Metabolismo Energético , Exercício Físico , Monitorização Ambulatorial/métodos , Gravidez , Autorrelato , Caminhada , Feminino , Humanos , Monitorização Ambulatorial/instrumentação , Atividade Motora , Reprodutibilidade dos Testes , Inquéritos e Questionários
14.
Pharmaceutics ; 13(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34684029

RESUMO

Foreskin, considered a biological waste material, has been shown to be a reservoir of therapeutic cells. The immunomodulatory properties of mesenchymal stromal/stem cells (MSCs) from the foreskin (FSK-MSCs) are being evaluated in cell-based therapy for degenerative, inflammatory and autoimmune disorders. Within the injured/inflamed tissue, proinflammatory lymphocytes such as IL-17-producing T helper cells (Th17) may interact with the stromal microenvironment, including MSCs. In this context, MSCs may encounter different levels of T cells as well as specific inflammatory signals. Uncovering the cellular and molecular changes during this interplay is central for developing an efficient and safe immunotherapeutic tool. To this end, an in vitro human model of cocultures of FSK-MSCs and T cells was established. These cocultures were performed at different cell ratios in the presence of an inflammatory setting. After confirming that FSK-MSCs respond to ISCT criteria by showing a typical phenotype and multilineage potential, we evaluated by flow cytometry the expression of Th17 cell markers IL-17A, IL23 receptor and RORγt within the lymphocyte population. We also measured 15 human Th17 pathway-related cytokines. Regardless of the T cell/MSC ratio, we observed a significant increase in IL-17A expression associated with an increase in IL-23 receptor expression. Furthermore, we observed substantial modulation of IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α secretion. These findings suggest that FSK-MSCs are receptive to their environment and modulate the T cell response accordingly. The changes within the secretome of the stromal and immune environment are likely relevant for the therapeutic effect of MSCs. FSK-MSCs represent a valuable cellular product for immunotherapeutic purposes that needs to be further clarified and developed.

15.
Toxicol Appl Pharmacol ; 247(1): 41-52, 2010 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-20576514

RESUMO

Extracts from plants containing plumbagin (PLB) continue to be used as a treatment of a number of chronic immunologically-based diseases. However, most of these claims are supported only by anecdotal evidence with few scientific reports describing the mechanism of action or the efficacy of plumbagin in the suppression of the immune response. In the current study, we tested the hypothesis that plumbagin-induced suppression of the immune response was mediated through the induction of apoptosis. Splenocytes from C57BL/6 mice cultured in the presence of 0.5 microM or greater concentrations of PLB significantly reduced proliferative responses to mitogens, including anti-CD3 mAbs, concanavalin A (Con A), lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) in vitro. Exposure of naïve and activated splenocytes to PLB led to a significant increase in the levels of apoptosis. In addition, PLB treatment led to a significant increase in the levels of reactive oxygen species (ROS) in naïve and activated splenocytes. Furthermore, treatment with the ROS scavenger, N-acetylcysteine (NAC), prevented PLB-induced apoptosis, suggesting a role of ROS in PLB-induced apoptosis. PLB-induced apoptosis led to ROS-mediated activation of both the extrinsic and intrinsic apoptotic pathways. In addition, plumbagin led to increased expression of Fas. Finally, treatment of mice with PLB (5mg/kg) led to thymic and splenic atrophy as well as a significant suppression of the response to SEB and dinitrofluorobenzene (DNFB) in vivo. Together, these results suggest that plumbagin has significant immunosuppressive properties which are mediated by generation of ROS, upregulation of Fas, and the induction of apoptosis.


Assuntos
Apoptose , Caspases/metabolismo , Imunossupressores/toxicidade , Linfócitos/efeitos dos fármacos , Naftoquinonas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Receptor fas/metabolismo , Acetilcisteína/metabolismo , Animais , Atrofia/induzido quimicamente , Dinitrofluorbenzeno/toxicidade , Enterotoxinas/toxicidade , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Cell Transplant ; 29: 963689720912707, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425073

RESUMO

Adult-derived human liver stem/progenitor cells (ADHLSCs) are a promising alternative to orthotopic liver transplantation in the treatment of inborn errors of metabolism. However, as is the case with many mesenchymal stromal cells, ADHLSCs have shown a low level of engraftment, which could be explained by the fact that they lack expression of selectin ligand and LFA-1 and only slightly express VLA- 4, molecules that have been shown to be involved in cell adhesion to the endothelium. In this paper, we have investigated strategies to increase their rolling and adhesion during the homing process by (1) adding a selectin ligand (Sialyl Lewis X) to their surface using biotinyl-N-hydroxy-succinimide-streptavidin bridges, and (2) protecting the adhesion proteins from trypsinization-induced damage using a thermosensitive polymer for cell culture and a nonenzymatic cell dissociation solution (CDS) for harvest. Despite increasing adhesion of ADHLSCs to E-selectin during an adhesion test in vitro performed under shear stress, the addition of Sialyl Lewis X did not increase adhesion to endothelial cells under the same conditions. Cultivating cells on a thermosensitive polymer and harvesting them with CDS increased their adhesion to endothelial cells under noninflammatory conditions, compared to the use of trypsin. However, we were not able to demonstrate any improvement in cell adhesion to the endothelium following culture on polymer and harvest with CDS, suggesting that alternative methods of improving engraftment still need to be evaluated.


Assuntos
Adesão Celular/fisiologia , Células Endoteliais/citologia , Endotélio/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Selectina E/metabolismo , Endotélio Vascular/citologia , Humanos , Neutrófilos/citologia
17.
Nutr J ; 8: 17, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19409085

RESUMO

BACKGROUND: Preventing weight gain rather than treating established obesity is an important economic and public health response to the rapidly increasing rates of obesity worldwide. Treatment of established obesity is complex and costly requiring multiple resources. Preventing weight gain potentially requires fewer resources to reach broad population groups, yet there is little evidence for successful interventions to prevent weight gain in the community. Women with children are an important target group because of high rates of weight gain and the potential to influence the health behaviors in family members. METHODS: The aim of this cluster randomized controlled trial was to evaluate the short term effect of a community-based self-management intervention to prevent weight gain. Two hundred and fifty mothers of young children (mean age 40 years +/- 4.5, BMI 27.9 kg/m2 +/- 5.6) were recruited from the community in Melbourne, Australia. The intervention group (n = 127) attended four interactive group sessions over 4 months, held in 12 local primary schools in 2006, and was compared to a group (n = 123) receiving a single, non-interactive, health education session. Data collection included self-reported weight (both groups), measured weight (intervention only), self-efficacy, dietary intake and physical activity. RESULTS: Mean measured weight decreased significantly in the intervention group (-0.78 kg 95% CI; -1.22 to -0.34, p < 0.001). Comparing groups using self-reported weight, both the intervention and comparison groups decreased weight, -0.75 kg (95% CI; -1.57 to 0.07, p = 0.07) and -0.72 kg (95% CI; -1.59 to 0.14 p = 0.10) respectively with no significant difference between groups (-0.03 kg, 95% CI; -1.32 to 1.26, p = 0.95). More women lost or maintained weight in the intervention group. The intervention group tended to have the greatest effect in those who were overweight at baseline and in those who weighed themselves regularly. Intervention women who rarely self-weighed gained weight (+0.07 kg) and regular self-weighers lost weight (-1.66 kg) a difference of -1.73 kg (95% CI; -3.35 to -0.11 p = 0.04). The intervention reported increased physical activity although the difference between groups did not reach significance. Both groups reported replacing high fat foods with low fat alternatives and self-efficacy deteriorated in the comparison group only. CONCLUSION: Both a single health education session and interactive behavioral intervention will result in a similar weight loss in the short term, although more participants in the interactive intervention lost or maintained weight. There were small non-significant changes to physical activity and changes to fat intake specifically replacing high fat foods with low fat alternatives such as fruit and vegetables. Self-monitoring appears to enhance weight loss when part of an intervention. TRIAL REGISTRATION: ACTRN12608000110381.


Assuntos
Dieta , Exercício Físico/fisiologia , Mães/psicologia , Obesidade/prevenção & controle , Autoeficácia , Adulto , Austrália , Análise por Conglomerados , Gorduras na Dieta/administração & dosagem , Exercício Físico/psicologia , Feminino , Frutas , Comportamentos Relacionados com a Saúde , Educação em Saúde , Humanos , Estilo de Vida , Mães/educação , Obesidade/psicologia , Prevenção Primária/métodos , Apoio Social , Verduras , Aumento de Peso , Redução de Peso , Saúde da Mulher
18.
Public Health Nutr ; 12(11): 2236-46, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19650959

RESUMO

OBJECTIVE: The WHO has recommended that prevention of overweight and obesity should begin early and target adults, including those with an acceptable BMI. The aim of the present paper was to systematically review published interventions with a specific stated aim to prevent weight gain. DESIGN: Five databases were searched to July 2008. The reference lists of review articles and obesity society meetings abstracts were hand searched. Interventions were included if the primary aim was to prevent weight gain and they included a comparison group. RESULTS: Ten publications were included, describing nine separate interventions in adults of various ages and target populations. All interventions incorporated diet and physical activity with behaviour change strategies. Most studies were between 1 and 3 years in duration. Five studies reported a significant difference in weight between intervention and control subjects of between 1.0 and 3.5 kg, due largely to an increase in weight in the control group. However, there was a lack of consistent, clear, psychological models and a failure to identify successful components. More intensive interventions were not always successful, nor were mail-only or clinic-based interventions. In contrast, interventions that included mixed modes of delivery with some personal contact were successful. CONCLUSIONS: There were relatively few trials aimed at the prevention of weight gain. Existing trials varied by intensity, delivery methods, target groups and study components, and therefore provide limited opportunities for comparison of effect size. Further large, effective, evidence-based programmes are urgently needed in the general population as well as high-risk groups.


Assuntos
Promoção da Saúde/métodos , Obesidade/prevenção & controle , Aumento de Peso , Adulto , Terapia Comportamental , Dieta , Exercício Físico , Comportamentos Relacionados com a Saúde , Humanos
19.
BMC Public Health ; 9: 2, 2009 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-19121220

RESUMO

BACKGROUND: Women aged 25-45 years represent a high risk group for weight gain and those with children are at increased risk because of weight gain associated with pregnancy and subsequent lifestyle change. Average self-reported weight gain is approximately 0.60 kg per year, and weight gain is associated with increased risk of chronic disease. There are barriers to reaching, engaging and delivering lifestyle interventions to prevent weight gain in this population. METHODS: This study investigated the baseline weight related behaviors and feasibility of recruiting and delivering a low intensity self-management lifestyle intervention to community based women with children in order to prevent weight gain, compared to standard education. The recruitment and delivery of the cluster-randomized controlled intervention was in conjunction with 12 primary (elementary) schools. Baseline data collection included demographic, anthropometric, behavioral and biological measures. RESULTS: Two hundred and fifty community based women were randomized as clusters to intervention (n = 127) or control (n = 123). Mean age was 40.4 years (SD 4.7) and mean BMI 27.8 kg/m2 (SD 5.6). All components of this intervention were successfully delivered and retention rates were excellent, 97% at 4 months.Nearly all women (90%) reported being dissatisfied with their weight and 72% attempted to self-manage their weight. Women were more confident of changing their diet (mean score 3.2) than physical activity (mean score 2.7). This population perceived they were engaging in prevention behaviors, with 71% reporting actively trying to prevent weight gain, yet they consumed a mean of 68 g fat/day (SD30 g) and 27 g saturated fat/day (SD12 g) representing 32% and 13% of energy respectively. The women had a high rate of dyslipidemia (33%) and engaged in an average of 9187 steps/day (SD 3671). CONCLUSION: Delivery of this low intensity intervention to a broad cross-section of community based women with children is feasible. Women with children are engaging in lifestyle behaviours which do not confer adequate health benefits. They appear to be motivated to attend prevention programs by their interest in weight management. Interventions are required to strengthen and sustain current attempts at achieving healthy lifestyle behaviours in women to prevent weight gain.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Comportamentos Relacionados com a Saúde , Estilo de Vida , Obesidade/prevenção & controle , Saúde da Mulher , Adulto , Antropometria , Austrália , Índice de Massa Corporal , Dieta , Exercício Físico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Obesidade/psicologia , Cooperação do Paciente/estatística & dados numéricos , Prevenção Primária/métodos , Características de Residência , Fatores de Risco , Resultado do Tratamento , Aumento de Peso , Redução de Peso
20.
BMC Public Health ; 9: 213, 2009 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-19563685

RESUMO

BACKGROUND: Lifestyle-related diseases, including diabetes, cardiovascular disease, and some cancers represent the greatest global health threat. Greater insight into health needs and beliefs, using broad community samples, is vital to reduce the burden of chronic disease. This study aimed to investigate gender, age, screening practices, health beliefs, and perceived future health needs for healthy ageing. METHODS: Random probability sampling using self-completion surveys in 1456 adults residing in Australia. RESULTS: Screening behaviors were associated with gender and age. Men and women >51 years were more likely (27%) to have screening health checks than those <50 years (2%). Factors nominated to influence health were lifestyle (92%), relationships (82%), and environment (80%). Women were more likely to nominate preparedness to have an annual health check, willingness to seek advice from their medical practitioner and to attend education sessions. Numerous health fears were associated with ageing, however participants were more likely to have a financial (72%) rather than a health plan (42%). More women and participants >51 years wanted information regarding illness prevention than men or those aged <30 years. CONCLUSION: Age and gender are associated with health related behaviors. Optimal health is perceived as a priority, yet often this perception is not translated into preventative action. These findings will inform future research and policy makers as we strive towards a healthier ageing society and the prevention of chronic disease.


Assuntos
Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Fatores Etários , Idoso , Austrália , Coleta de Dados , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Serviços Preventivos de Saúde/estatística & dados numéricos , Fatores Sexuais
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