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1.
Microbes Infect ; 26(1-2): 105243, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38380604

RESUMEN

Pteropine orthoreovirus (PRV) causes respiratory tract infections in humans. Despite its emergence as a zoonotic and respiratory virus, little is known about its cell tropism, which hampers progress in fully understanding its pathogenesis in humans. Hek293 cells are most susceptible to PRV infection, while HeLa cells are the least. Human cytokeratin 1 (CK1) was identified as the protein that interacts with PRV. The immunofluorescence assay and qPCR results revealed prior treatment with anti-CK1 may provide Hek293 cells protection against PRV. The KRT1-knockout Hek293 cells were less susceptible to PRV infection. Further study into the pathogenesis of PRV in humans is needed.


Asunto(s)
Enfermedades de los Peces , Orthoreovirus , Infecciones por Reoviridae , Animales , Humanos , Células HEK293 , Células HeLa , Queratinas , Infecciones por Reoviridae/patología
2.
Artículo en Inglés | MEDLINE | ID: mdl-35682035

RESUMEN

Dengue is a vector-borne disease affected by meteorological factors and is commonly recorded from ground stations. Data from ground station have limited spatial representation and accuracy, which can be overcome using satellite-based Earth Observation (EO) recordings instead. EO-based meteorological recordings can help to provide a better understanding of the correlations between meteorological variables and dengue cases. This paper aimed to first validate the satellite-based (EO) data of temperature, wind speed, and rainfall using ground station data. Subsequently, we aimed to determine if the spatially matched EO data correlated with dengue fever cases from 2011 to 2019 in Malaysia. EO data were spatially matched with the data from four ground stations located at states and districts in the central (Selangor, Petaling) and east coast (Kelantan, Kota Baharu) geographical regions of Peninsular Malaysia. Spearman's rank-order correlation coefficient (ρ) was performed to examine the correlation between EO and ground station data. A cross-correlation analysis with an eight-week lag period was performed to examine the magnitude of correlation between EO data and dengue case across the three time periods (2011-2019, 2015-2019, 2011-2014). The highest correlation between the ground-based stations and corresponding EO data were reported for temperature (mean ρ = 0.779), followed by rainfall (mean ρ = 0.687) and wind speed (mean ρ = 0.639). Overall, positive correlations were observed between weekly dengue cases and rainfall for Selangor and Petaling across all time periods with significant correlations being observed for the period from 2011 to 2019 and 2015 to 2019. In addition, positive significant correlations were also observed between weekly dengue cases and temperature for Kelantan and Kota Baharu across all time periods, while negative significant correlations between weekly dengue cases and temperature were observed in Selangor and Petaling across all time periods. Overall negative correlations were observed between weekly dengue cases and wind speed in all areas from 2011 to 2019 and 2015 to 2019, with significant correlations being observed for the period from 2015 to 2019. EO-derived meteorological variables explained 48.2% of the variation in dengue cases in Selangor. Moderate to strong correlations were observed between meteorological variables recorded from EO data derived from satellites and ground stations, thereby justifying the use of EO data as a viable alternative to ground stations for recording meteorological variables. Both rainfall and temperature were found to be positively correlated with weekly dengue cases; however, wind speed was negatively correlated with dengue cases.


Asunto(s)
Dengue , Dengue/epidemiología , Humanos , Incidencia , Malasia/epidemiología , Conceptos Meteorológicos , Temperatura , Viento
3.
Bio Protoc ; 11(9): e4005, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-34124305

RESUMEN

The COVID-19 pandemic requires mass screening to identify those infected for isolation and quarantine. Individually screening large populations for the novel pathogen, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is costly and requires a lot of resources. Sample pooling methods improve the efficiency of mass screening and consume less reagents by increasing the capacity of testing and reducing the number of experiments performed, and are therefore especially suitable for under-developed countries with limited resources. Here, we propose a simple, reliable pooling strategy for COVID-19 testing using clinical nasopharyngeal (NP) and/or oropharyngeal (OP) swabs. The strategy includes the pooling of 10 NP/OP swabs for extraction and subsequent testing via quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and may also be applied to the screening of other pathogens.

4.
Parasit Vectors ; 14(1): 315, 2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34112220

RESUMEN

Dengue fever is the most important mosquito-borne viral disease in Southeast Asia. Insecticides remain the most effective vector control approach for Aedes mosquitoes. Four main classes of insecticides are widely used for mosquito control: organochlorines, organophosphates, pyrethroids and carbamates. Here, we review the distribution of dengue fever from 2000 to 2020 and its associated mortality in Southeast Asian countries, and we gather evidence on the trend of insecticide resistance and its distribution in these countries since 2000, summarising the mechanisms involved. The prevalence of resistance to these insecticides is increasing in Southeast Asia, and the mechanisms of resistance are reported to be associated with target site mutations, metabolic detoxification, reduced penetration of insecticides via the mosquito cuticle and behavioural changes of mosquitoes. Continuous monitoring of the status of resistance and searching for alternative control measures will be critical for minimising any unpredicted outbreaks and improving public health. This review also provides improved insights into the specific use of insecticides for effective control of mosquitoes in these dengue endemic countries.


Asunto(s)
Aedes/efectos de los fármacos , Dengue/epidemiología , Resistencia a los Insecticidas , Insecticidas/farmacología , Larva/efectos de los fármacos , Mosquitos Vectores/efectos de los fármacos , Animales , Asia Sudoriental , Humanos , Insecticidas/clasificación , Larva/virología , Mosquitos Vectores/virología , Organofosfatos/farmacología , Prevalencia
5.
Front Pharmacol ; 12: 631136, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33833681

RESUMEN

Edible bird's nest (EBN) is recognized as a nourishing food among Chinese people. The efficacy of EBN was stated in the records of traditional Chinese medicine and its activities have been reported in many researches. Malaysia is the second largest exporter of EBNs in the world, after Indonesia. For many years, EBN trade to China was not regulated until August 2011, when a safety alert was triggered for the consumption of EBNs. China banned the import of EBNs from Malaysia and Indonesia due to high level of nitrite. Since then, the Malaysia government has formulated Malaysia Standards for swiftlet farming (MS 2273:2012), edible bird's nest processing plant design and management (MS 2333:2010), and edible bird's nest product quality (MS 2334:2011) to enable the industry to meet the specified standards for the export to China. On the other hand, Indonesia's EBN industry formulated a standard operating procedure (SOP) for exportation to China. Both countries can export EBNs to China by complying with the standards and SOPs. EBN contaminants may include but not limited to nitrite, heavy metals, excessive minerals, fungi, bacteria, and mites. The possible source of contaminants may come from the swiftlet farms and the swiftlets or introduced during processing, storage, and transportation of EBNs, or adulterants. Swiftlet house design and management, and EBN processing affect the bird's nest color. Degradation of its optical quality has an impact on the selling price, and color changes are tied together with nitrite level. In this review, the current and future prospects of EBNs in Malaysia and Indonesia in terms of their quality, and the research on the contaminants and their effects on EBN color changes are discussed.

6.
Nanomaterials (Basel) ; 11(2)2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33669327

RESUMEN

Plastics have enormous impacts to every aspect of daily life including technology, medicine and treatments, and domestic appliances. Most of the used plastics are thrown away by consumers after a single use, which has become a huge environmental problem as they will end up in landfill, oceans and other waterways. These plastics are discarded in vast numbers each day, and the breaking down of the plastics from micro- to nano-sizes has led to worries about how toxic these plastics are to the environment and humans. While, there are several earlier studies reported the effects of micro- and nano-plastics have on the environment, there is scant research into their impact on the human body at subcellular or molecular levels. In particular, the potential of how nano-plastics move through the gut, lungs and skin epithelia in causing systemic exposure has not been examined thoroughly. This review explores thoroughly on how nanoplastics are created, how they behave/breakdown within the environment, levels of toxicity and pollution of these nanoplastics, and the possible health impacts on humans, as well as suggestions for additional research. This paper aims to inspire future studies into core elements of micro- and nano-plastics, the biological reactions caused by their specific and unusual qualities.

7.
Surg Oncol ; 37: 101536, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33677364

RESUMEN

INTRODUCTION: Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. The aim of our study is to determine whether this large variant is different from the usual fibroadenoma in terms of its biological pathways and biomarkers. METHODS: mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas. RESULTS: A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy. CONCLUSION: Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas de Ciclo Celular/fisiología , Fibroadenoma/genética , Fibroadenoma/patología , Transducción de Señal/fisiología , Adolescente , Adulto , Algoritmos , Colágeno Tipo V , Femenino , Factores de Crecimiento de Fibroblastos , Fibronectinas , Perfilación de la Expresión Génica , Humanos , Subunidad p19 de la Interleucina-23 , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Receptor 1 de Factores de Crecimiento Endotelial Vascular , Adulto Joven
8.
PLoS One ; 15(8): e0238417, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32857823

RESUMEN

The rapid global spread of the coronavirus disease (COVID-19) has inflicted significant health and socioeconomic burden on affected countries. As positive cases continued to rise in Malaysia, public health laboratories experienced an overwhelming demand for COVID-19 screening. The confirmation of positive cases of COVID-19 has solely been based on the detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) using real-time reverse transcription polymerase chain reaction (qRT-PCR). In efforts to increase the cost-effectiveness and efficiency of COVID-19 screening, we evaluated the feasibility of pooling clinical Nasopharyngeal/Oropharyngeal (NP/OP) swab specimens during nucleic acid extraction without a reduction in sensitivity of qRT-PCR. Pools of 10 specimens were extracted and subsequently tested by qRT-PCR according to the WHO-Charité protocol. We demonstrated that the sample pooling method showed no loss of sensitivity. The effectiveness of the pooled testing strategy was evaluated on both retrospective and prospective samples, and the results showed a similar detection sensitivity compared to testing individual sample alone. This study demonstrates the feasibility of using a pooled testing strategy to increase testing capacity and conserve resources, especially when there is a high demand for disease testing.


Asunto(s)
Infecciones por Coronavirus/diagnóstico , Tamizaje Masivo/métodos , Neumonía Viral/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Manejo de Especímenes/métodos , Betacoronavirus , COVID-19 , Humanos , Malasia , Nasofaringe/virología , Orofaringe/virología , Pandemias , SARS-CoV-2 , Sensibilidad y Especificidad
9.
Polymers (Basel) ; 12(8)2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32824514

RESUMEN

Being biodegradable and biocompatible are crucial characteristics for biomaterial used for medical and biomedical applications. Vegetable oil-based polyols are known to contribute both the biodegradability and biocompatibility of polyurethanes; however, petrochemical-based polyols were often incorporated to improve the thermal and mechanical properties of polyurethane. In this work, palm oil-based polyester polyol (PPP) derived from epoxidized palm olein and glutaric acid was reacted with isophorone diisocyanate to produce an aliphatic polyurethane, without the incorporation of any commercial petrochemical-based polyol. The effects of water content and isocyanate index were investigated. The polyurethanes produced consisted of > 90% porosity with interconnected micropores and macropores (37-1700 µm) and PU 1.0 possessed tensile strength and compression stress of 111 kPa and 64 kPa. The polyurethanes with comparable thermal stability, yet susceptible to enzymatic degradation with 7-59% of mass loss after 4 weeks of treatment. The polyurethanes demonstrated superior water uptake (up to 450%) and did not induce significant changes in pH of the medium. The chemical changes of the polyurethanes after enzymatic degradation were evaluated by FTIR and TGA analyses. The polyurethanes showed cell viability of 53.43% and 80.37% after 1 and 10 day(s) of cytotoxicity test; and cell adhesion and proliferation in cell adhesion test. The polyurethanes produced demonstrated its potential as biomaterial for soft tissue engineering applications.

10.
Cancers (Basel) ; 12(7)2020 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-32664564

RESUMEN

Pancreatic cancer ranks high among the causes of cancer-related mortality. The prognosis of this grim condition has not improved significantly over the past 50 years, despite advancement in imaging techniques, cancer genetics and treatment modalities. Due to the relative difficulty in the early detection of pancreatic tumors, as low as 20% of patients are eligible for potentially curative surgery; moreover, chemotherapy and radiotherapy (RT) do not confer a great benefit in the overall survival of the patients. Currently, emerging developments in immunotherapy have yet to bring a significant clinical advantage among pancreatic cancer patients. In fact, pancreatic tumor-driven immune evasion possesses one of the greatest challenges leading to immunotherapeutic resistance. Most of the immune escape pathways are innate, while poor priming of hosts' immune response and immunoediting constitute the adaptive immunosuppressive machinery. In this review, we extensively discuss the pathway perturbations undermining the anti-tumor immunity specific to pancreatic cancer. We also explore feasible up-and-coming therapeutic strategies that may restore immunity and address therapeutic resistance, bringing hope to eliminate the status quo in pancreatic cancer prognosis.

11.
Environ Health ; 19(1): 37, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32245482

RESUMEN

BACKGROUND: Malaysia has the highest rate of diabetes mellitus (DM) in the Southeast Asian region, and has ongoing air pollution and periodic haze exposure. METHODS: Diabetes data were derived from the Malaysian National Health and Morbidity Surveys conducted in 2006, 2011 and 2015. The air pollution data (NOx, NO2, SO2, O3 and PM10) were obtained from the Department of Environment Malaysia. Using multiple logistic and linear regression models, the association between long-term exposure to these pollutants and prevalence of diabetes among Malaysian adults was evaluated. RESULTS: The PM10 concentration decreased from 2006 to 2014, followed by an increase in 2015. Levels of NOx decreased while O3 increased annually. The air pollutant levels based on individual modelled air pollution exposure as measured by the nearest monitoring station were higher than the annual averages of the five pollutants present in the ambient air. The prevalence of overall diabetes increased from 11.4% in 2006 to 21.2% in 2015. The prevalence of known diabetes, underdiagnosed diabetes, overweight and obesity also increased over these years. There were significant positive effect estimates of known diabetes at 1.125 (95% CI, 1.042, 1.213) for PM10, 1.553 (95% CI, 1.328, 1.816) for O3, 1.271 (95% CI, 1.088, 1.486) for SO2, 1.124 (95% CI, 1.048, 1.207) for NO2, and 1.087 (95% CI, 1.024, 1.153) for NOx for NHMS 2006. The adjusted annual average levels of PM10 [1.187 (95% CI, 1.088, 1.294)], O3 [1.701 (95% CI, 1.387, 2.086)], NO2 [1.120 (95% CI, 1.026, 1.222)] and NOx [1.110 (95% CI, 1.028, 1.199)] increased significantly from NHMS 2006 to NHMS 2011 for overall diabetes. This was followed by a significant decreasing trend from NHMS 2011 to 2015 [0.911 for NO2, and 0.910 for NOx]. CONCLUSION: The findings of this study suggest that long-term exposure to O3 is an important associated factor of underdiagnosed DM risk in Malaysia. PM10, NO2 and NOx may have mixed effect estimates towards the risk of DM, and their roles should be further investigated with other interaction models. Policy and intervention measures should be taken to reduce air pollution in Malaysia.


Asunto(s)
Contaminación del Aire/efectos adversos , Diabetes Mellitus/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Contaminantes Atmosféricos/análisis , Diabetes Mellitus/etiología , Femenino , Humanos , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Material Particulado/análisis , Prevalencia , Adulto Joven
12.
Med Mycol ; 58(3): 333-340, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-31309220

RESUMEN

Cladosporium is one of the most abundant spore. Fungi of this genus can cause respiratory allergy and intrabronchial lesion. We studied the differential expression of host genes after the interaction of Cladosporium sphaerospermum conidia with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B cells or HPAEpiC cells for 48 hours respectively. This culture duration was chosen as it was associated with high germination rate. RNA was extracted from two biological replicates per treatment. RNA of BEAS-2B cells was used to assess changes in gene expression using AffymetrixGeneChip® Human Transcriptome Array 2.0. After co-culture with Cladosporium spores, 68 individual genes were found differentially expressed (P ≤ 0.05) and up-regulated ≥ 1.5 folds while 75 genes were found differentially expressed at ≤ -1.5 folds compared with controls. Reverse transcription and qPCR were performed on the RNA collected from both BEAS-2B cells and HPAEpiC cells to validate the microarray results with 7 genes. Based on the findings, infected pulmonary epithelial cells exhibited an increase in cell death-related genes and genes associated with innate immunity.


Asunto(s)
Células Epiteliales Alveolares/microbiología , Cladosporium/patogenicidad , Perfilación de la Expresión Génica , Interacciones Microbiota-Huesped/genética , Alveolos Pulmonares/microbiología , Bronquios/citología , Bronquios/microbiología , Línea Celular , Humanos , Análisis por Micromatrices , Alveolos Pulmonares/citología , Regulación hacia Arriba
13.
J Exp Clin Cancer Res ; 38(1): 162, 2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-30987642

RESUMEN

BACKGROUND: Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME). MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME. CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.


Asunto(s)
Huésped Inmunocomprometido , Inmunomodulación/efectos de los fármacos , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/terapia , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/inmunología , Fibroblastos Asociados al Cáncer/metabolismo , Estudios Clínicos como Asunto , Terapia Combinada , Humanos , Inmunoterapia , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Terapia Molecular Dirigida , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Resultado del Tratamiento
15.
PLoS One ; 12(9): e0184802, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28910372

RESUMEN

OBJECTIVE: The aim of this study was to investigate the correlations between serum cartilage oligomeric matrix protein (COMP), interleukin-16 (IL-16) and different grades of knee osteoarthritis (KOA) in Malaysian subjects. METHODS: Ninety subjects were recruited comprising 30 with Kellgren-Lawrence (K-L) grade 2 KOA, 27 with K-L grade 3 KOA, 7 with grade 4 KOA, and 30 healthy controls. All subjects completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Serum COMP and IL-16 levels were measured using ELISA and their values log transformed to ensure a normal distribution. RESULTS: There was no significant differences in levels of log serum COMP and IL-16 between healthy controls and KOA patients. There were no significant differences in the log serum COMP and IL-16 levels within the different K-L grades in the KOA patients. In KOA patients, log serum IL-16 levels significantly correlated with the WOMAC score (p = 0.001) and its subscales, pain (p = 0.005), stiffness (p = 0.019) and physical function (p<0.0001). Serum IL-16 levels were significantly higher in Malaysian Indians compared to Malays and Chinese (p = 0.024). CONCLUSIONS: In this multi-ethnic Malaysian population, there was no difference in serum COMP and IL-16 levels between healthy controls and patients with KOA, nor was there any difference in serum COMP or IL-16 levels across the various K-L grades of KOA. However, there were significant inter-racial differences in serum IL-16 levels.


Asunto(s)
Proteína de la Matriz Oligomérica del Cartílago/sangre , Interleucina-6/sangre , Osteoartritis de la Rodilla/metabolismo , Anciano , Pueblo Asiatico/etnología , Femenino , Humanos , Malasia/etnología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/etnología , Proyectos Piloto , Índice de Severidad de la Enfermedad
16.
Oncotarget ; 7(36): 57633-57650, 2016 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-27192118

RESUMEN

Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.


Asunto(s)
Neoplasias de la Mama/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Neoplasias de la Mama/diagnóstico , Línea Celular Tumoral , Supervivencia Celular , Doxorrubicina/química , Femenino , Silenciador del Gen , Humanos , Células MCF-7 , Fosforilación , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/metabolismo , Transducción de Señal
17.
Artículo en Inglés | MEDLINE | ID: mdl-26429550

RESUMEN

Widespread food poisoning due to microbial contamination has been a major concern for the food industry, consumers and governing authorities. This study is designed to determine the levels of fungal contamination in edible bird nests (EBNs) using culture and molecular techniques. Raw EBNs were collected from five house farms, and commercial EBNs were purchased from five Chinese traditional medicine shops (companies A-E) in Peninsular Malaysia. The fungal contents in the raw and commercial EBNs, and boiled and unboiled EBNs were determined. Culturable fungi were isolated and identified. In this study, the use of these methods revealed that all EBNs had fungal colony-forming units (CFUs) that exceeded the limit set by Standards and Industrial Research Institute of Malaysia (SIRIM) for yeast and moulds in EBNs. There was a significant difference (p < 0.05) in the number of types of fungi isolated from raw and commercial EBNs, but no significant difference in the reduction of the number of types of fungi after boiling the EBNs (p > 0.05). The types of fungi isolated from the unboiled raw EBNs were mainly soil, plant and environmental fungi, while the types of fungi isolated from the boiled raw EBNs, unboiled and boiled commercial EBNs were mainly environmental fungi. Aspergillus sp., Candida sp., Cladosporium sp., Neurospora sp. and Penicillum sp. were the most common fungi isolated from the unboiled and boiled raw and commercial EBNs. Some of these fungi are mycotoxin producers and cause opportunistic infections in humans. Further studies to determine the mycotoxin levels and methods to prevent or remove these contaminations from EBNs for safe consumption are necessary. The establishment and implementation of stringent regulations for the standards of EBNs should be regularly updated and monitored to improve the quality of the EBNs and consumer safety.


Asunto(s)
Aspergillus/aislamiento & purificación , Candida/aislamiento & purificación , Cladosporium/aislamiento & purificación , Micotoxinas/aislamiento & purificación , Neurospora/aislamiento & purificación , Penicillium/aislamiento & purificación , Animales , Aspergillus/clasificación , Aspergillus/genética , Aves/fisiología , Candida/clasificación , Candida/genética , Cladosporium/clasificación , Cladosporium/genética , Recuento de Colonia Microbiana , ADN de Hongos/genética , Contaminación de Alimentos/análisis , Análisis de Peligros y Puntos de Control Críticos/métodos , Humanos , Malasia , Comportamiento de Nidificación/fisiología , Neurospora/clasificación , Neurospora/genética , Valor Nutritivo , Penicillium/clasificación , Penicillium/genética
18.
Trans R Soc Trop Med Hyg ; 107(11): 672-83, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24123127

RESUMEN

This study aimed to synthesize available evidence on the extent of malaria and soil-transmitted intestinal helminth (STH) co-infections in people living in endemic countries and to explore the effect of interactions between malaria and STHs on anemia. We searched relevant studies in electronic databases up to March 2013. Studies comparing malaria and STH co-infected patients with those not co-infected were included and the effect estimates were pooled using a random-effects model. We identified 30 studies for meta-analyses of which 17 were cross-sectional design. The majority of included studies (80%) were carried out in African countries. Among pregnant women, those infected with hookworm were found to have higher association with malaria infection compared with those without (summary OR: 1.36; 95% CI: 1.17-1.59; I(2): 0%). Among non-pregnant adults, the summary OR of the association between anemia and the combined malaria and STH was 2.91 (1.38-6.14). The summary OR of the association between anemia and malaria alone was 1.53 (0.97-2.42), while the association between anemia and STH alone was 0.28 (0.04-1.95). There is no good evidence to support a different effect of malaria and STH on anemia. A subgroup analysis showed a higher risk of malaria infection in the primigravidae (summary OR: 1.61; 95% CI: 1.3-1.99; I(2): 0%). In conclusion, the malaria-STH co-infection was variable with complex outcomes on anemia.


Asunto(s)
Anemia/epidemiología , Helmintiasis/complicaciones , Parasitosis Intestinales/complicaciones , Malaria/complicaciones , Adolescente , Adulto , África/epidemiología , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/etiología , Animales , Niño , Preescolar , Coinfección , Estudios Transversales , Femenino , Helmintiasis/sangre , Helmintiasis/epidemiología , Humanos , Parasitosis Intestinales/sangre , Parasitosis Intestinales/epidemiología , Malaria/sangre , Malaria/epidemiología , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones Parasitarias del Embarazo/sangre , Complicaciones Parasitarias del Embarazo/epidemiología , Prevalencia , Suelo/parasitología , Adulto Joven
19.
Lung ; 191(1): 27-34, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23180033

RESUMEN

BACKGROUND: Extrapulmonary tuberculosis has been an AIDS-defining condition. Individual studies that highlight the association between HIV and extrapulmonary TB are available. Our objectives were to synthesis evidence on the association between extrapulmonary tuberculosis and HIV and to explore the effective preventive measures of these two diseases. METHODS: This is a meta-analysis of observational studies reporting effect estimates on how HIV is associated with extrapulmonary tuberculosis. We searched for the eligible studies in the electronic databases using search terms related to HIV and extrapulmonary tuberculosis. Where possible, we estimated the summary odds ratios using random effects meta-analysis. We stratified analysis by the type of study design. We assessed heterogeneity of effect estimates within each group of studies was assessed using I (2) test. RESULTS: Nineteen studies (7 case control studies and 12 cohort studies) were identified for the present study. The pooled analysis shows a significant association between HIV and extrapulmonary tuberculosis (summary odds ratio: 1.3; 95 % confidence interval (CI) 1.05-1.6; I (2): 0 %). In a subgroup analysis with two studies, a significant association was found between CD4+ count less than 100 and the incidence of extrapulmonary tuberculosis (summary OR: 1.31; 95 % CI 1.02-1.68; I (2): 0 %). CONCLUSIONS: Findings show evidence on the association between extrapulmonary tuberculosis and HIV, based on case control studies. Further studies to understand the mechanisms of interaction of the two pathogens are recommended.


Asunto(s)
Infecciones por VIH/epidemiología , Tuberculosis Gastrointestinal/epidemiología , Tuberculosis Pleural/epidemiología , Tuberculosis Urogenital/epidemiología , Comorbilidad , VIH/fisiología , Humanos , Mycobacterium tuberculosis/fisiología , Diseño de Software
20.
BMC Res Notes ; 5: 201, 2012 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-22537619

RESUMEN

BACKGROUND: Angiogenesis has been reported to be one of the contributory factors to the pathogenesis of psoriasis vulgaris. This study aims to compare the expression of different angiogenesis growth factors namely (1) the vascular endothelial growth factor (VEGF) subfamily: A, B, C, D and placenta growth factor (PlGF); (2) nerve growth factor (NGF) and (3) von Willebrand factor (vWFr) in the skins of patients with psoriasis vulgaris and non-psoriatic volunteers. RESULTS: Comparative immunohistochemistry study was performed on the paraffin-sectioned psoriatic and healthy skins with the abovementioned markers. VEGF-C (p = 0.016) and NGF (p = 0.027) were expressed intensely in the cases when compared with the controls. The NGF was the only marker that was solely expressed in the cases and absent in all the controls. CONCLUSION: The NGF (angiogenesis) and VEGF-C (lymphangiogenesis) might play a crucial role in the pathogenesis of psoriasis vulgaris and could be researched further as potential new targeted therapies for psoriasis vulgaris.


Asunto(s)
Factor de Crecimiento Nervioso/biosíntesis , Psoriasis/metabolismo , Piel/metabolismo , Factor C de Crecimiento Endotelial Vascular/biosíntesis , Adulto , Biomarcadores/análisis , Femenino , Humanos , Inmunohistoquímica , Linfangiogénesis , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Factor de Crecimiento Placentario , Proteínas Gestacionales/biosíntesis , Piel/irrigación sanguínea , Piel/patología , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor B de Crecimiento Endotelial Vascular/biosíntesis , Factor D de Crecimiento Endotelial Vascular/biosíntesis , Adulto Joven , Factor de von Willebrand/biosíntesis
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