Naresuan University Journal
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Mitochondrial mass, a new metabolic biomarker for stem-like cancer cells: Understanding WNT/FGF-driven anabolic signaling.
No full textHere, we developed an isogenic cell model of "stemness" to facilitate protein biomarker discovery in breast cancer. For this purpose, we used knowledge gained previously from the study of the mouse mammary tumor virus (MMTV). MMTV initiates mammary tumorigenesis in mice by promoter insertion adjacent to two main integration sites, namely Int-1 (Wnt1) and Int-2 (Fgf3), which ultimately activates Wnt/β-catenin signaling, driving the propagation of mammary cancer stem cells (CSCs). Thus, to develop a humanized model of MMTV signaling, we over-expressed WNT1 and FGF3 in MCF7 cells, an ER(+) human breast cancer cell line. We then validated that MCF7 cells over-expressing both WNT1 and FGF3 show a 3.5-fold increase in mammosphere formation, and that conditioned media from these cells is also sufficient to promote stem cell activity in untransfected parental MCF7 and T47D cells, as WNT1 and FGF3 are secreted factors. Proteomic analysis of this model system revealed the induction of i) EMT markers, ii) mitochondrial proteins, iii) glycolytic enzymes and iv) protein synthesis machinery, consistent with an anabolic CSC phenotype. MitoTracker staining validated the expected WNT1/FGF3-induced increase in mitochondrial mass and activity, which presumably reflects increased mitochondrial biogenesis. Importantly, many of the proteins that were up-regulated by WNT/FGF-signaling in MCF7 cells, were also transcriptionally over-expressed in human breast cancer cells in vivo, based on the bioinformatic analysis of public gene expression datasets of laser-captured patient samples. As such, this isogenic cell model should accelerate the discovery of new biomarkers to predict clinical outcome in breast cancer, facilitating the development of personalized medicine.Finally, we used mitochondrial mass as a surrogate marker for increased mitochondrial biogenesis in untransfected MCF7 cells. As predicted, metabolic fractionation of parental MCF7 cells, via MitoTracker staining, indicated that high mitochondrial mass is a new metabolic biomarker for the enrichment of anabolic CSCs, as functionally assessed by mammosphere-forming activity. This observation has broad implications for understanding the role of mitochondrial biogenesis in the propagation of stem-like cancer cells. Technically, this general metabolic approach could be applied to any cancer type, to identify and target the mitochondrial-rich CSC population.The implications of our work for understanding the role of mitochondrial metabolism in viral oncogenesis driven by random promoter insertions are also discussed, in the context of MMTV and ALV infections
Anatomical relations of anterior and posterior ankle arthroscopy portals: a cadaveric study.
No full textBACKGROUND: Ankle arthroscopy is an increasingly used technique. Knowledge of the anatomical structures in relation to its portals is paramount to avoid complications. METHODS: Twenty cadaveric ankles were analysed to assess the distance between relevant neurovascular structures to the anteromedial, anterolateral, posteromedial, and posterolateral arthroscopy portals. RESULTS: The intermediate dorsal branch of the superficial peroneal nerve was the closest structure to any of the portals (4.8 mm from the anterolateral portal), followed by the posterior tibial nerve (7.3 mm from the posteromedial portal). All structures analysed but one (posterior tibial artery) were, at least in one specimen
The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers.
No full textOBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers
The effects of consumer cultural values on the image congruence of “IKEA” and Chinese consumers
No full textPrevalence of chronic pulmonary aspergillosis in patients with tuberculosis from Iran.
No full textIn patients with preexisting lung disease, especially a cavity, Aspergillus can infect the surface of the cavity, causing chronic cavitary pulmonary aspergillosis (CCPA), and may form an aspergilloma, collectively called chronic pulmonary aspergillosis (CPA). In the present study, we assessed tuberculosis (TB) patients for CPA based on culture and serological methods. During a period of 1 year (from March 2013 to March 2014), we studied 124 patients with TB (94 with current TB and 30 with previous TB) at Masih Daneshvari Hospital in Tehran, Iran. Sputum specimens were analyzed by direct microscopic examination (DME) and fungal culture. The clinical and radiological features of all patients were recorded, to categorize the patients into CCPA and aspergilloma. All patients were screened for serum-specific IgG against A. fumigatus, by enzyme-linked immunosorbent assay (ELISA). Out of 124 patients with TB (66 male, age range: 10-91 years), 48 patients (38.7 %) exhibited residual cavities. Eighteen (14.5 %) patients had cavities with pleural thickening. A round-shaped mass lesion was detected in six patients (6.8 %). DME was positive in ten patients for septate fungal hyphae. A. fumigatus was grown from 14 samples. Fifty-five (44.3 %) cases were positive for serum-specific IgG against A. fumigatus. Of 124 patients with TB, 3 (2.4 %) met criteria for aspergilloma and 14 (11.3 %) for CCPA. CPA is a common clinical presentation in individuals with healed TB in Iran, as reported by previous studies from other countries
Russia's cumulative carbon budgets for a global 2°C target
No full textRussia is the fifth highest emitter of carbon dioxide, and has been in the top five for at least six decades. However, thus far no in-depth study has estimated Russia's cumulative emissions in the context of the global 2°C constraint. This is despite the Intergovernmental Panel on Climate Change (IPCC) reiterating the importance of cumulative emissions and their approximately linear correlation with temperature rises. Translating the global 2°C temperature commitment into a meaningful national context, this paper derives and evaluates 2°C-compatible carbon budgets for Russia, based on a range of apportionment regimes. The work contributes to the debate by providing a deeper analysis of the principles of allocating carbon emissions to Russia, while considering two probabilities for remaining within 2°C. This analysis demonstrates how, if Russia is to make a fair contribution to global emission reductions in line with 2°C, its 2011-2100 cumulative emissions should not exceed 20-26 GtCO2, commensurate with a 37-52% probability of exceeding the global 2°C commitment. If Russia continues to emit CO2 at current annual levels, this budget will be 'spent' by the mid-2020s. Yet, the carbon budget estimated here for Russia appears technically feasible, if extremely challenging. Despite continuing to assert itself as a fossil fuel superpower, Russia has a wealth of opportunities for full and early decarbonisation, including the potential to become a net exporter of renewable energy
A randomised double-blind placebo-controlled 12- week feasibility trial of methotrexate added to treatment as usual in early schizophrenia: study protocol for a randomised controlled trial.
No full textBACKGROUND: Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. There is growing evidence that inflammatory processes are involved in the pathogenesis of schizophrenia. In our recent randomised double-blind placebo-controlled clinical trial in Pakistan and Brazil, the addition of minocycline (antibiotic and anti-inflammatory drug) for 1 year to treatment as usual reduced negative symptoms and improved some cognitive measures. A meta-analysis of cytokine changes in the peripheral blood has identified IL-2, IFN-gamma, TNF-alpha and soluble IL-2 receptor as trait markers of schizophrenia because their levels were elevated during acute exacerbations and reduced in remission. This suggests immune activation and an inflammatory syndrome in schizophrenia. Based on the evidence of the strong anti-inflammatory properties of methotrexate, we propose that low-dose methotrexate may be an effective therapy in early schizophrenia. METHODS/DESIGN: This is a double-blind placebo-controlled study of methotrexate added to treatment as usual for patients suffering from schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder. This will be with 72 patients, 36 in each arm over 3 months. There will be screening, randomisation and follow-up visits. Full clinical assessments will be carried out at baseline, 2, 4, 8 and 12 weeks. Social and cognitive assessments will be carried out at baseline and 12 weeks. Methotrexate will be given at a dose of 10 mgs orally once a week for a 3-month period. DISCUSSION: Evidence suggests inflammatory processes are involved in the pathogenesis of schizophrenia and anti-inflammatory treatments have shown to have some beneficial effects. Methotrexate is a known immunosuppressant and anti-inflammatory drug. The aim of this study is to establish the degree of improvement in positive and negative symptoms, as well as cognitive functioning with the addition of methotrexate to treatment as usual.ClinicalTrials.gov identifier: NCT02074319 (24 February 2014)
Ex vivo evaluation of acellular and cellular collagen-glycosaminoglycan flowable matrices.
No full textCollagen-glycosaminoglycan flowable matrices (CGFM) are increasingly finding utility in a diversifying number of cutaneous surgical procedures. Cellular in-growth and vascularisation of CGFM remain rate-limiting steps, increasing cost and decreasing efficacy. Through in vitro and ex vivo culture methods, this study investigated the improvement of injectable CGFM by the incorporation of hyaluronan (HA) and viable human cells (primary human dermal fibroblasts (PHDFs) and bone marrow-derived mesenchymal stem cells (BM-MSCs)). Ex vivo investigations included the development and evaluation of a human cutaneous wound healing model for the comparison of dermal substitutes. Cells mixed into the Integra Flowable Wound Matrix (IFWM), a commercially available CGFM, were confirmed to be viable and proliferative through MTT assays (p
How Chronic Pain May Change Your Brain
No full textNew research on people with arthritis suggests that the ability to withstand more pain may be an adaptive response. In a small new study, published Friday in the journal Pain, researchers used brain imaging on 17 people with arthritis and nine people without who served as controls. The researchers were trying to better understand the underlining reasons why there appears to be variability in pain tolerance, which could provide insights for people dealing with chronic pain.The researchers looked specifically at the prevalence of receptors in the brain that respond to natural opiates like endorphins—feel-good chemicals in the brain often released during hard exercise, stress, orgasm and pain.When the researchers used heat on the men and women’s skin to induce pain, they found that the more opioid receptors they had, the greater their ability to handle pain. These receptors were higher among the people with arthritis, which the researchers say suggests that this increase is an adaptive response, possibly to make it easier to deal with the chronic pain that comes with such a condition.The researchers did not prove that arthritis pain increases the numbers of these receptors, but lead study author Christopher Brown, a senior research associate at the University of Cambridge, said in a statement that “although the mechanisms of these adaptive changes are unknown, if we can understand how we can enhance them, we may find ways of naturally increasing resilience to pain without the side effects associated with many pain-killing drugs.”The study was small and more research is needed, but the finding suggests it may be worthwhile to look for future interventions that enhance natural defense mechanisms to pain