10 research outputs found
The correlation of EMT and p53 immunohistochemical markers with cisplatin resistance in muscle invasive bladder cancer patients:A single-centred study
INTRODUCTION: Although epithelial-mesenchymal transition (EMT) and p53 have been established to play a pivotal role in the aggressiveness of muscle-invasive bladder cancer (MIBC), its pathological correlation to cisplatin treatment in the Malaysian patient cohort is lacking. This study aimed to evaluate the association of EMT markers, e-cadherin, vimentin and actin, as well as tumour suppressor gene, p53, in cisplatin-receiving MIBC patients. MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53. RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case. CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.</p
Food manifested communication of traditional knowledge among tribal women in Tamil Nadu
391-397Every culture has its own traditional food practice. In the recent past, the traditional food practices and the transfer of knowledge have been in transition. A study was conducted among women tribes in Kolli Hills, Pachamalai Hills and Pechiparai in Tamilnadu to assess the Traditional Food Knowledge (TFK) of tribal women and their transmission through generations. A total number of 66 women from these three tribal and hill areas were selected randomly for this study. This study explores unique traditional food knowledge, practices and their present day adaptations and how they had used their traditional food for communicating their indigenous knowledge. A self-structured questionnaire, FGD and in-depth interviews were conducted to understand the tribe‘s perception towards traditional food and communication. The results revealed that food practices in three different places were not the same and not consistent in Pachamalai. Impacts of modern food habits among the tribes were also seen in the results
Doxorubicin-Resistant TNBC Cells Exhibit Rapid Growth with Cancer Stem Cell-like Properties and EMT Phenotype, Which Can Be Transferred to Parental Cells through Autocrine Signaling
Emerging evidence suggests that breast cancer stem cells (BCSCs), and epithelial–mesenchymal transition (EMT) may be involved in resistance to doxorubicin. However, it is unlear whether the doxorubicin-induced EMT and expansion of BCSCs is related to cancer dormancy, or outgrowing cancer cells with maintaining resistance to doxorubicin, or whether the phenotypes can be transferred to other doxorubicin-sensitive cells. Here, we characterized the phenotype of doxorubicin-resistant TNBC cells while monitoring the EMT process and expansion of CSCs during the establishment of doxorubicin-resistant MDA-MB-231 human breast cancer cells (DRM cells). In addition, we assessed the potential signaling associated with the EMT process and expansion of CSCs in doxorubicin-resistance of DRM cells. DRM cells exhibited morphological changes from spindle-shaped MDA-MB-231 cells into round-shaped giant cells. They exhibited highly proliferative, EMT, adhesive, and invasive phenotypes. Molecularly, they showed up-regulation of Cyclin D1, mesenchymal markers (β-catenin, and N-cadherin), MMP-2, MMP-9, ICAM-1 and down-regulation of E-cadherin. As the molecular mechanisms responsible for the resistance to doxorubicin, up-regulation of EGFR and its downstream signaling, were suggested. AKT and ERK1/2 expression were also increased in DRM cells with the advancement of resistance to doxorubicin. Furthermore, doxorubicin resistance of DRM cells can be transferred by autocrine signaling. In conclusion, DRM cells harbored EMT features with CSC properties possessing increased proliferation, invasion, migration, and adhesion ability. The doxorubicin resistance, and doxorubicin-induced EMT and CSC properties of DRM cells, can be transferred to parental cells through autocrine signaling. Lastly, this feature of DRM cells might be associated with the up-regulation of EGFR
Activated ERK Signaling Is One of the Major Hub Signals Related to the Acquisition of Radiotherapy-Resistant MDA-MB-231 Breast Cancer Cells
Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. In this study, we performed antibody array analysis to identify the hub signaling mechanism for the radiation resistance of RT-R-MDA-MB-231 cells by comparing parental MDA-MB-231 (p-MDA-MB-231) and RT-R-MDA-MB-231 cells. Antibody array analysis unveiled that the MAPK1 protein was the most upregulated protein in RT-R-MDA-MB-231 cells compared to in p-MDA-MB-231 cells. The pathway enrichment analysis also revealed the presence of MAPK1 in almost all enriched pathways. Thus, we used an MEK/ERK inhibitor, PD98059, to block the MEK/ERK pathway and to identify the role of MAPK1 in the radio-resistance of RT-R-MDA-MB-231 cells. MEK/ERK inhibition induced cell death in both p-MDA-MB-231 and RT-R-MDA-MB-231 cells, but the death mechanism for each cell was different; p-MDA-MB-231 cells underwent apoptosis, showing cell shrinkage and PARP-1 cleavage, while RT-R-MDA-MB-231 cells underwent necroptosis, showing mitochondrial dissipation, nuclear swelling, and an increase in the expressions of CypA and AIF. In addition, MEK/ERK inhibition reversed the radio-resistance of RT-R-MDA-MB-231 cells and suppressed the increased expression of CSC markers (CD44 and OCT3/4) and the EMT phenotype (β-catenin and N-cadherin/E-cadherin). Taken together, this study suggests that activated ERK signaling is one of the major hub signals related to the radio-resistance of MDA-MB-231 breast cancer cells
The relationship between biventricular myocardial performance and metabolic parameters during incremental exercise and recovery in healthy adolescents
This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Background left ventricular (LV) and right ventricular (RV) myocardial reserve during exercise in adolescents has not been directly characterized. The aim of this study was to quantify myocardial performance response to exercise by using two-dimensional (2-D) speckle tracking echocardiography and describe the relationship between myocardial reserve, respiratory, and metabolic exercise parameters. A total of 23 healthy boys and girls (mean age 13.2 ± 2.7 yr; stature 159.1 ± 16.4 cm; body mass 49.5 ± 16.6 kg; BSA 1.47 ± 0.33 m(2)) completed an incremental cardiopulmonary exercise test (25 W·3 min increments) with simultaneous acquisition of 2-D transthoracic echocardiography at rest, each exercise stage up to 100 W, and in recovery at 2 min and 10 min. Two-dimensional LV (LV Sl) and RV (RV Sl) longitudinal strain and LV circumferential strain (LV Sc) were analyzed to define the relationship between myocardial performance reserve and metabolic exercise parameters. Participants achieved a peak oxygen uptake (V̇o2peak) of 40.6 ± 8.9 ml·kg(-1)·min(-1) and a work rate of 154 ± 42 W. LV Sl and LV Sc and RV Sl increased significantly across work rates (P < 0.05). LV Sl during exercise was significantly correlated to resting strain, V̇o2peak, oxygen pulse, and work rate (0.530 ≤ r ≤ 0.784, P < 0.05). This study identifies a positive and moderate relationship between LV and RV myocardial performance and metabolic parameters during exercise by using a novel methodology. Relationships detected present novel data directly describing myocardial adaptation at different stages of exercise and recovery that in the future can help directly assess cardiac reserve in patients with cardiac pathology.The study was supported by the University of Exeter and the Bristol NIHR Biomedical Research Unit for Cardiovascular Disease. It was funded by a David Telling and an Above & Beyond project grant. G. Pieles holds a National Institute for Health Research Academic Clinical Lectureship
Artemisia annua L. Polyphenol-Induced Cell Death Is ROS-Independently Enhanced by Inhibition of JNK in HCT116 Colorectal Cancer Cells
c-Jun N-terminal kinase (JNK) is activated by chemotherapeutic reagents including natural plant polyphenols, and cell fate is determined by activated phospho-JNK as survival or death depending on stimuli and cell types. The purpose of this study was to elucidate the role of JNK on the anticancer effects of the Korean plant Artemisia annua L. (pKAL) polyphenols in p53 wild-type HCT116 human colorectal cancer cells. Cell morphology, protein expression levels, apoptosis/necrosis, reactive oxygen species (ROS), acidic vesicles, and granularity/DNA content were analyzed by phase-contrast microscopy; Western blot; and flow cytometry of annexin V/propidium iodide (PI)-, dichlorofluorescein (DCF)-, acridine orange (AO)-, and side scatter pulse height (SSC-H)/DNA content (PI)-stained cells. The results showed that pKAL induced morphological changes and necrosis or late apoptosis, which were associated with loss of plasma membrane/Golgi integrity, increased acidic vesicles and intracellular granularity, and decreased DNA content through downregulation of protein kinase B (Akt)/β-catenin/cyclophilin A/Golgi matrix protein 130 (GM130) and upregulation of phosphorylation of H2AX at Ser-139 (γ-H2AX)/p53/p21/Bak cleavage/phospho-JNK/p62/microtubule-associated protein 1 light chain 3B (LC3B)-I. Moreover, JNK inhibition by SP600125 enhanced ROS-independently pKAL-induced cell death through downregulation of p62 and upregulation of p53/p21/Bak cleavage despite a reduced state of DNA damage marker γ-H2AX. These findings indicate that phospho-JNK activated by pKAL inhibits p53-dependent cell death signaling and enhances DNA damage signaling, but cell fate is determined by phospho-JNK as survival rather than death in p53 wild-type HCT116 cells
Food manifested communication of traditional knowledge among tribal women in Tamil Nadu
Every culture has its own traditional food practice. In the recent past, the traditional food practices and the transfer of knowledge have been in transition. A study was conducted among women tribes in Kolli Hills, Pachamalai Hills and Pechiparai in Tamilnadu to assess the Traditional Food Knowledge (TFK) of tribal women and their transmission through generations. A total number of 66 women from these three tribal and hill areas were selected randomly for this study. This study explores unique traditional food knowledge, practices and their present day adaptations and how they had used their traditional food for communicating their indigenous knowledge. A self-structured questionnaire, FGD and in-depth interviews were conducted to understand the tribe’s perception towards traditional food and communication. The results revealed that food practices in three different places were not the same and not consistent in Pachamalai. Impacts of modern food habits among the tribes were also seen in the results.
Core outcome set for research studies evaluating treatments for twin–twin transfusion syndrome
Objective
To develop, using a Delphi procedure and a nominal group technique, a core outcome set (COS) for studies evaluating treatments for twin–twin transfusion syndrome (TTTS), which should assist in standardizing outcome selection, collection and reporting in future research studies.
Methods
An international steering group comprising healthcare professionals, researchers and patients with experience of TTTS guided the development of this COS. Potential core outcomes, identified through a comprehensive literature review and supplemented by outcomes suggested by the steering group, were entered into a three‐round Delphi survey. Healthcare professionals, researchers, and patients or relatives of patients who had experienced TTTS were invited to participate. Consensus was defined a priori using the 15%/70% definition of the Core Outcome Measures in Effectiveness Trials (COMET) initiative. The modified nominal group technique was used to evaluate the consensus outcomes in a face‐to‐face consultation meeting and identify the final COS.
Results
One hundred and three participants, from 29 countries, participated in the three‐round Delphi survey. Of those, 88 completed all three rounds. Twenty‐two consensus outcomes were identified through the Delphi procedure and entered into the modified nominal group technique. The consensus meeting was attended by 11 healthcare professionals, two researchers and three patients; 12 core outcomes were prioritized for inclusion in the COS. Fetal core outcomes included live birth, pregnancy loss (including miscarriage, stillbirth, termination of pregnancy and neonatal mortality), subsequent death of a cotwin following single‐twin demise at the time of treatment, recurrence of TTTS, twin anemia–polycythemia syndrome and amniotic band syndrome. Neonatal core outcomes included gestational age at delivery, birth weight, brain injury syndromes and ischemic limb injury. Maternal core outcomes included maternal mortality and admission to Level‐2 or ‐3 care setting. One aspirational outcome, neurodevelopment at 18–24 months of age, was also prioritized.
Conclusions
Implementing the COS for TTTS within future research studies could make a substantial contribution to advancing the usefulness of research in TTTS. Standardized definitions and measurement instruments are now required for individual core outcomes
Microorganismos endófitos presentes en las especies vegetales del género vaccinium como productores de metabolitos secundarios con potencial farmacológico.
Los microorganismos endófitos se encuentran en los espacios intercelulares de las plantas
sin generar daño alguno, es así como se presenta una asociación mutualista endófito-
planta, donde la planta brinda nutrición y hospedaje al endófito y a cambio ésta recibe
beneficios para su supervivencia, lo anterior gracias a que los endófitos poseen la
capacidad de producir metabolitos secundarios que le confieren a la planta diversas
propiedades. Además, existen estudios que demuestran que estos metabolitos también
tienen aplicaciones en el ámbito de la medicina.
El género Vaccinium está compuesto por diferentes especies entre las cuales se encuentran
V. angustifolium, V. corymbosum y V. myrtillus, que son conocidas como arándanos y se
distribuyen a nivel mundial; en Latinoamérica se encuentra la especie V. meridionale y es
llamada comúnmente ‘‘mortiño’’. Estas plantas se destacan por producir metabolitos
secundarios que le confieren propiedades antioxidantes y antimicrobianas, así mismo
características medicinales, ya que actúan como antidiabéticos y antitumorales. Estos
metabolitos también pueden ser producidos o estimulados por las comunidades endófitas
presentes en las plantas, por lo cual son una gran alternativa para el desarrollo de nuevos
medicamentos o cuidados paliativos para enfermedades que suelen presentar
complicaciones o reacciones secundarias a los tratamientos comunes.
En la presente revisión se profundizó en los diferentes microorganismos endófitos
descritos en el género Vaccinium, así como los metabolitos secundarios producidos por los
mismos, donde se pudo establecer que los metabolitos secundarios de los endófitos como
son candidatos potenciales para el tratamiento de diferentes enfermedades por medio del
desarrollo de nuevos medicamentos.Endophytic microorganisms are found in the intercellular spaces of plants without causing
any damage, this is how an endophyte-plant mutualistic association occurs, where the plant
provides nutrition and harbors the endophyte and in return it receives benefits for its
survival, the above thanks because endophytes have the ability to produce secondary
metabolites that confer various properties to the plant. In addition, there are studies that
show that these metabolites also have applications in the field of medicine.
The genus Vaccinium is made up of different species, including V. angustifolium, V.
corymbosum and V. myrtillus, which are known as blueberries and are distributed
worldwide; the species V. meridionale is present only in Latin America and it is known as
"mortiño". These plants stand out for producing secondary metabolites that confer
antioxidant and antimicrobial properties, as well as other medicinal characteristics, since
they act as antidiabetic and antitumor agents. These metabolites can also be produced or
stimulated by endophytic communities present in plants, which is why they are a great
alternative for the development of new drugs or palliative care for diseases that usually
present complications or secondary reactions to common treatments.
In the present review, the different endophytic microorganisms described in the Vaccinium
genus were studied in depth, as well as the secondary metabolites produced by them,
where it was established that endophyte secondary metabolites are potential candidates for
the treatment of different diseases by means of the development of new drugs.1. Introducción 12
2. Objetivos 15
2.1 Objetivo general
2.2 Objetivos específicos
3. Antecedentes 16
4. Marco teórico 24
4.1
Endófitos 24
4.2 Metabolitos
secundarios 28
4.3 Género
Vaccinium 35
4.3.1 Mortiño 35
4.3.2 Arandano 38
4.4 Actividad antioxidante 40
4.4.1 Radicales libres 41
4.4.2 Antioxidantes 42
4.4.2.1
Polifenoles 42
4.4.2.1.1
Flavonoides 43
4.4.2.1.2 Proantocianidinas (Taninos condensados) 44
4.4.2.1.3
Antocianinas 45
4.4.2.2 Acido ascorbico (VitaminaC) 46
4.5 Microorganismos endófitos presentes en el género Vaccinium como fuentede fármacos 46
4.6 Microorganismos endófitos y actividad antioxidante 49
5. Diseño metodológico 51
5.1 Tipo de investigación 51
5.2 Universo 51
5.3 Población 51
5.4 Muestra 51
5.5 Métodos 52
5.5.1 Revisión de información existente 52
5.5.2 Selección del material bibliográfico de acuerdo a la temática a tratar 52
5.5.3 Estructuración coherente del documento 53
6. Resultados 53
6.1 Fase 1. Búsqueda y revisión de la información 53
6.2 Fase 2. Selección del material bibliográfico 57
6.3 Fase 3. Organización lógica del documento 58
6.4 Fase 4. Analisis de la información 58
7. Discusión 63
8. Conclusiones 69
9. Recomendaciones 70
10. Bibliografía 71
AnexosPregradoBacteriólogo(a) y Laboratorista Clínic
