100 research outputs found
Impact of CoQ10, L-Carnitine and Cocktail Antioxidants on Oxidative Stress Markers in HIV Patients — Mini Review and Clinical Trial
Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells
<p>Abstract</p> <p>Background</p> <p>Methotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment with methotrexate is limited by the development of drug resistance, which may be acquired through different ways. To get insights into the mechanisms associated with drug resistance and sensitization we performed a functional analysis of genes deregulated in methotrexate resistant cells, either due to its co-amplification with the <it>dhfr </it>gene or as a result of a transcriptome screening using microarrays.</p> <p>Methods</p> <p>Gene expression levels were compared between triplicate samples from either HT29 sensitive cells and resistant to 10<sup>-5 </sup>M MTX by hybridization to the GeneChip<sup>® </sup>HG U133 PLUS 2.0 from Affymetrix. After normalization, a list of 3-fold differentially expressed genes with a p-value < 0.05 including multiple testing correction (Benjamini and Hochberg false discovery rate) was generated. RT-Real-time PCR was used to validate the expression levels of selected genes and copy-number was determined by qPCR. Functional validations were performed either by siRNAs or by transfection of an expression plasmid.</p> <p>Results</p> <p>Genes adjacent to the <it>dhfr locus </it>and included in the 5q14 amplicon were overexpressed in HT29 MTX-resistant cells. Treatment with siRNAs against those genes caused a slight reduction in cell viability in both HT29 sensitive and resistant cells. On the other hand, microarray analysis of HT29 and HT29 MTX resistant cells unveiled overexpression of caveolin 1, enolase 2 and PKCα genes in resistant cells without concomitant copy number gain. siRNAs against these three genes effectively reduced cell viability and caused a decreased MTX resistance capacity. Moreover, overexpression of E-cadherin, which was found underexpressed in MTX-resistant cells, also sensitized the cells toward the chemotherapeutic agent. Combined treatments targeting siRNA inhibition of caveolin 1 and overexpression of E-cadherin markedly reduced cell viability in both sensitive and MTX-resistant HT29 cells.</p> <p>Conclusion</p> <p>We provide functional evidences indicating that caveolin 1 and E-cadherin, deregulated in MTX resistant cells, may play a critical role in cell survival and may constitute potential targets for coadjuvant therapy.</p
Impact of storage conditions on preparation of activated carbon from sheep wool fibres
Received: January 31st, 2023 ; Accepted: June 16th, 2023 ; Published: July 6th, 2023 ; Correspondence: [email protected] the European Union, up to 200 thousand tons (Zoccola et al., 2015) of sheep wool
fibres, that are not used for textile fabrication, are a secondary by-product with wide field of
application possibilities, including preparation of activated carbon. Taking into account, that wool
fibres can be stored for long time, under impact of the local climate conditions (including low
temperatures) before their application, for example, under variety of temperature, presence of air
and light, different moisture conditions, it is necessary to estimate the impact of wool’s storage
conditions on the preparation of activated carbon. In the present work, various parameters, such
as, temperature, presence of air and daylight as well as humidity, were selected for comparison.
After storage of wool fibres under selected various conditions, thermogravimetry/differential
thermal analysis (TG/DTA) followed by with Fourier transform infrared (FTIR) spectrometry
were used in order to estimate the impact of each parameter on the thermal decomposition
processes: release of moisture, sulphur and nitrogen containing compounds and oxidative
degradation followed by release of carbon dioxide. It was estimated, that one year of storage
under varying conditions does not significantly affect the thermal decomposition properties of
the wool fibres. However, minor impact of humidity absorbed from air on wool is observed. Wool
samples that were stored at elevated humidity gave higher residual carbon yield (R) in comparison
to the fibres stored in dry conditions. The obtained results are used to develop recommendations
for preparation of activated carbon from wool fibres and for its application in air filtrating
systems
Building capacity for dementia care in Latin America and the Caribbean
Latin America and the Caribbean (LAC) have limited facilities and professionals trained to diagnose, treat, and support people with dementia and other forms of cognitive impairment. The situation for people with dementia is poor, and worsening as the proportion of elderly in the general population is rapidly expanding. We reviewed existing initiatives and provided examples of actions taken to build capacity and improve the effectiveness of individuals, organizations, and national systems that provide treatment and support for people with dementia and their caregivers. Regional barriers to capacity building and the importance of public engagement are highlighted. Existing programs need to disseminate their objectives, accomplishments, limitations, and overall lessons learned in order to gain greater recognition of the need for capacity-building programs
Pharmacological and Clinical Effectiveness of Zingiber officinale and Alpinia galanga in Patients with Osteoarthritis
Molecular heterogeneity of large-conductance calcium-activated potassium channels in canine intracardiac ganglia
Large conductance calcium-activated potassium (BK) channels are widely expressed in the nervous system. We have recently shown that principal neurons from canine intracardiac ganglia (ICG) express a paxilline- and TEA-sensitive BK current, which increases neuronal excitability. In the present work, we further explore the molecular constituents of the BK current in canine ICG. We found that the β1 and β4 regulatory subunits are expressed in ICG. Single channel voltage-dependence at different calcium concentrations suggested that association of the BKα with a particular β subunit was not enough to explain the channel activity in this tissue. Indeed, we detected the presence of several splice variants of the BKα subunit. In conclusion, BK channels in canine ICG may result from the arrangement of different BKα splice variants, plus accessory β subunits. The particular combinations expressed in canine IC neurons likely rule the excitatory role of BK current in this tissue
Automated synthesis of transmission lines loaded with complementary split ring resonators (CSRRs) and open complementary split ring resonators (OCSRRs) through aggressive space mapping (ASM)
This paper is focused on the application of space mapping optimization to the automated synthesis of
transmission lines loaded with complementary split ring resonators (CSRRs) and open complementary split ring resonators (OCSRRs). These structures are of interest for the implementation of resonant-type metamaterial transmission lines and for the design of planar microwave circuits based on such complementary resonators. The paper presents a method to generate the layouts of CSRR- and
OCSRR-loaded microstrip lines from the elements of their equivalent circuit models. Using the so-called aggressive space mapping, a specific implementation that uses quasi-Newton type iteration, we have developed synthesis algorithms that are able to provide the topology of these CSRR and OCSRR-loaded lines in few steps. The most relevant aspect, however, is that this synthesis process is completely
automatic, i.e., it does not require any action from the designers, other than initiating the algorithm. Moreover, this technique can be translated to other electrically small planar elements described by lumped element equivalent circuit models.This work has been partially supported by MICIIN-Spain (Projects TEC2010-17512 METATRANSFER, TEC2010-21520-C04-01 AVANSAT, CONSOLIDER EMET CSD2008-00066, and Grant AP2008-04707), Generalitat de Catalunya (Project 2009SGR-421), and MITyC-Spain (Project TSI-020100-2010-169 METASINTESIS). Ferran Martin is in debt to ICREA for supporting his work through an ICREA Academia Award (calls 2008 and 2013).Selga, J.; Rodríguez Pérez, AM.; Orellana, M.; Boria Esbert, VE.; Martín, F. (2014). Automated synthesis of transmission lines loaded with complementary split ring resonators (CSRRs) and open complementary split ring resonators (OCSRRs) through aggressive space mapping (ASM). Applied Physics A. 117(2):557-565. https://doi.org/10.1007/s00339-014-8703-xS5575651172G.V. Eleftheriades, K.G. Balmain, Negative Refraction Metamaterials: Fundamental Principles and Applications (Wiley, New Jersey, 2005)C. Caloz, T. Itoh, Electromagnetic Metamaterials: Transmission Line Theory and Microwave Applications (Wiley, New Jersey, 2006)R. Marqués, F. Martín, M. Sorolla, Metamaterials with Negative Parameters: Theory, Design and Microwave Applications (Wiley, New Jersey, 2008)F. Martín, Artificial Transmission Lines for RF and Microwave Applications. (Wiley, New Jersey) (to be published)M.A. Antoniades, G.V. Eleftheriades, A broadband series power divider using zero-degree metamaterial phase shifting lines. IEEE Microw. Wirel. Compon. Lett. 15, 808–810 (2005)H. Okabe, C. Caloz, T. Itoh, A compact enhanced bandwidth hybrid ring using an artificial lumped element left handed transmission line section. IEEE Trans. Microw. Theory Tech. 52, 798–804 (2004)G. Sisó, J. Bonache, M. Gil, F. Martín, Application of resonant-type metamaterial transmission lines to the design of enhanced bandwidth components with compact dimensions. Microw. Opt. Technol. Lett. 50, 127–134 (2008)I.H. Lin, M. De Vincentis, C. Caloz, T. Itoh, Arbitrary dual-band components using composite right/left handed transmission lines. IEEE Trans. Microw. Theory Tech. 52, 1142–1149 (2004)A.C. Papanastasiou, G.E. Georghiou, G.V. Eleftheriades, A quad-band Wilkinson power divider using generalized NRI transmission lines. IEEE Microw. Wirel. Compon. Lett. 18, 521–523 (2008)M. Durán-Sindreu, G. Sisó, J. Bonache, F. Martín, Planar multi-band microwave components based on the generalized composite right/left handed transmission line concept. IEEE Trans. Microw. Theory Tech. 58(12), 3882–3891 (2010)J. Bonache, I. Gil, J. García-García, F. Martín, Novel microstrip band pass filters based on complementary split ring resonators. IEEE Trans. Microw. Theory Tech. 54, 265–271 (2006)M. Gil, J. Bonache, J. García-García, J. Martel, F. Martín, Composite right/left handed (CRLH) metamaterial transmission lines based on complementary split rings resonators (CSRRs) and their applications to very wide band and compact filter design. IEEE Trans. Microw. Theory Tech. 55, 1296–1304 (2007)S. Lim, C. Caloz, T. Itoh, Metamaterial-based electronically-controlled transmission line structure as a novel leaky-wave antenna with tunable angle and beamwidth. IEEE Trans. Microw. Theory Tech. 52(12), 2678–2690 (2004)G. Zamora, S. Zuffanelli, F. Paredes, F. Javier Herraiz-Martínez, F. Martín, J. Bonache, Fundamental mode leaky-wave-antenna (LWA) using slot line and split-ring-resonator (SRR) based metamaterials. IEEE Antennas Wirel. Propag. Lett. 12, 1424–1427 (2013)A.K. Iyer, G.V. Eleftheriades, Negative refractive index metamaterials supporting 2-D waves. in IEEE-MTT Int’l Microwave Symposium, vol 2, Seattle, WA, pp. 412–415 (2002)A.A. Oliner, A periodic-structure negative-refractive-index medium without resonant elements. In URSI Digest, IEEE-AP-S USNC/URSI National Radio Science Meeting, San Antonio, TX, pp. 41 (2002)C. Caloz, T. Itoh, Application of the transmission line theory of left-handed (LH) materials to the realization of a microstrip LH transmission line. in Proceedings of IEEE-AP-S USNC/URSI National Radio Science Meeting, vol 2, San Antonio, TX, pp. 412–415 (2002)F. Martín, F. Falcone, J. Bonache, R. Marqués, M. Sorolla, Split ring resonator based left handed coplanar waveguide. Appl. Phys. Lett. 83, 4652–4654 (2003)F. Falcone, T. Lopetegi, M.A.G. Laso, J.D. Baena, J. Bonache, R. Marqués, F. Martín, M. Sorolla (2004) Babinet principle applied to the design of metasurfaces and metamaterials. Phys. Rev. Lett. 93, paper 197401M. Durán-Sindreu, A. Vélez, F. Aznar, G. Sisó, J. Bonache, F. Martín, Application of open split ring resonators and open complementary split ring resonators to the synthesis of artificial transmission lines and microwave passive components. IEEE Trans. Microw. Theory Tech. 57, 3395–3403 (2009)A. Vélez, F. Aznar, M. Durán-Sindreu, J. Bonache, F. Martín, Stop-band and band-pass filters in coplanar waveguide technology implemented by means of electrically small metamaterial-inspired open resonators. IET Microw. Antennas Propag. 4, 712–716 (2004)J.D. Baena, J. Bonache, F. Martín, R. Marqués, F. Falcone, T. Lopetegi, M.A.G. Laso, J. García, I. Gil, M. Flores-Portillo, M. Sorolla, Equivalent circuit models for split ring resonators and complementary split rings resonators coupled to planar transmission lines. IEEE Trans. Microw. Theory Tech. 53, 1451–1461 (2005)M. Gil, J. Bonache, J. Selga, J. García-García, F. Martín, Broadband resonant type metamaterial transmission lines. IEEE Microw. Wirel. Compon. Lett. 17, 97–99 (2007)M. Durán-Sindreu, P. Vélez, J. Bonache, F. Martín, Broadband microwave filters based on open split ring resonators (OSRRs) and open complementary split ring resonators (OCSRRs): improved models and design optimization. Radioengineering 20, 775–783 (2011)P. Vélez, J. Naqui, M. Durán-Sindreu, J. Bonache, F. Martín, Broadband microstrip bandpass filter based on open complementary split ring resonators. Int. J. Antennas Propag. 2012, 6 (2012)J.W. Bandler, R.M. Biernacki, S.H. Chen, P.A. Grobelny, R.H. Hemmers, Space mapping technique for electromagnetic optimization. IEEE Trans. Microw. Theory Tech. 42, 2536–2544 (1994)J.W. Bandler, R.M. Biernacki, S.H. Chen, R.H. Hemmers, K. Madsen, Electromagnetic optimization exploiting aggressive space mapping. IEEE Trans. Microw. Theory Tech. 43, 2874–2882 (1995)J.W. Bandler, Q.S. Cheng, S.A. Dakroury, A.S. Mohamed, M.H. Bakr, K. Madsen, J. Søndergaard, Space mapping: the state of the art. IEEE Trans. Microw. Theory Tech. 52, 337–361 (2004)C.G. Broyden, A class of methods for solving nonlinear simultaneous equations. Math. Comput. 19(92), 577–593 (1965)J. Selga, A. Rodríguez, V.E. Boria, F. Martín, Synthesis of split rings based artificial transmission lines through a new two-step, fast converging, and robust aggressive space mapping (ASM) algorithm. IEEE Trans. Microw. Theory Tech. 61(6), 2295–2308 (2013)A. Velez, F. Aznar, J. Bonache, M.C. Velázquez-Ahumada, J. Martel, F. Martín, Open complementary split ring resonators (OCSRRs) and their application to wideband CPW band pass filters. IEEE Microw. Wirel. Compon. Lett. 19, 197–199 (2009)D.M. Bates, D.G. Watts, Nonlinear Regression Analysis and Its Applications (Wiley, New York, 1998
Impact of treatment on damage and hospitalization in elderly patients with microscopic polyangiitis and granulomatosis with polyangiitis
OBJECTIVE: Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown. METHODS: Consecutive patients from Sweden, England, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide, rituximab, and corticosteroids the first three months was registered. Outcomes up to two years from diagnosis included vasculitis damage index (VDI), hospitalization, and cause of death. RESULTS: Treatment data was available for 167 of 202 patients. At two years, 4% had no items of damage. There was a positive association between VDI score at two years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using cyclophosphamide or rituximab. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. MPO-ANCA positivity and lower creatinine levels decreased the odds for readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose. CONCLUSION: Immunosuppressive treatment with cyclophosphamide or rituximab in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first three months was associated with treatment-related damage and fatal infections
Overexpression of S100A4 in human cancer cell lines resistant to methotrexate
Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The
efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of
MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate
strategy to prevent the development of this resistance.
Methods: The differential expression pattern between sensitive and MTX-resistant cells was determined by whole
human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the
studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant
cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively.
Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA
against S100A4. Transfection of an expression vector encoding for β-catenin was used to inquire for the possible
transcriptional regulation of S100A4 through the Wnt pathway.
Results: S100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this
gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused
desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a
chemosensitization in combined treatments with MTX. β-catenin overexpression experiments support a possible
involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells.
Conclusions: S100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of
HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both
approaches highlight a role for S100A4 in MTX resistanc
Extra Virgin Olive Oil Contains a Phenolic Inhibitor of the Histone Demethylase LSD1/KDM1A
The lysine-specific histone demethylase 1A (LSD1) also known as lysine (K)-specific
demethylase 1A (KDM1A) is a central epigenetic regulator of metabolic reprogramming in
obesity-associated diseases, neurological disorders, and cancer. Here, we evaluated the ability
of oleacein, a biophenol secoiridoid naturally present in extra virgin olive oil (EVOO), to target
LSD1. Molecular docking and dynamic simulation approaches revealed that oleacein could target
the binding site of the LSD1 cofactor flavin adenosine dinucleotide with high affinity and at low
concentrations. At higher concentrations, oleacein was predicted to target the interaction of LSD1
with histone H3 and the LSD1 co-repressor (RCOR1/CoREST), likely disturbing the anchorage of
LSD1 to chromatin. AlphaScreen-based in vitro assays confirmed the ability of oleacein to act as
a direct inhibitor of recombinant LSD1, with an IC50 as low as 2.5 umol/L. Further, oleacein fully
suppressed the expression of the transcription factor SOX2 (SEX determining Region Y-box 2) in cancer
stem-like and induced pluripotent stem (iPS) cells, which specifically occurs under the control of an
LSD1-targeted distal enhancer. Conversely, oleacein failed to modify ectopic SOX2 overexpression
driven by a constitutive promoter. Overall, our findings provide the first evidence that EVOO contains
a naturally occurring phenolic inhibitor of LSD1, and support the use of oleacein as a template to
design new secoiridoid-based LSD1 inhibitors.Work in the Menendez laboratory is supported by the Spanish Ministry of Science and Innovation
(Grant SAF2016-80639-P, Plan Nacional de l+D+I, founded by the European Regional Development Fund, Spain)
and by an unrestricted research grant from the Fundació Oncolliga Girona (Lliga catalana d’ajuda al malalt de
càncer, Girona). The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21)
and the Generalitat Valenciana (PROMETEO/2016/006) supports work in the Encinar laborator
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