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Article: Synergistic influence of cytokine gene polymorphisms over the risk of dementia: A multifactor dimensionality reduction analysis.

Juárez-Cedillo, Teresa / Martínez-Rodríguez, Nancy / Vargas-Alarcon, Gilberto / Juárez-Cedillo, Enrique / Valle-Medina, Antonio / Garrido-Acosta, Osvaldo / Ramirez, Alfredo

Frontiers in aging neuroscience

2022 Volume 14, Page(s) 952173

Abstract: Objective: Evidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma ( ... ...

Abstract	Objective: Evidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma (IFN-γ) on the susceptibility to the development of dementia. Materials and methods: In the study, 221 patients diagnosed with dementia and 710 controls were included. The multifactor-dimensionality reduction (MDR) analysis was performed to identify the epistasis between SNP located in genes of IL-α (rs1800587), IL-6 (rs1800796), TNFα (rs361525 and rs1800629), and IFNγ (rs2069705). The best risk prediction model was identified based on precision and cross-validation consistency. Results: Multifactor-dimensionality reduction analysis detected a significant model with the genes TNFα, IFNγ, IL1α, and IL6 (prediction success: 72%, Conclusion: These data indicate that gene-gene interactions form significant models to identify populations susceptible to dementia.
Language	English
Publishing date	2022-10-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2022.952173
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Article ; Online: Reduction of inappropriate prescriptions in older adults through the support of Asynchronous Geriatric Counseling Online (AGAlink): Implemented in primary care.

Avalos-Mejia, Annia Marisol / García-Cruz, Juan Carlos / Escobedo de la Peña, Jorge / Garrido-Acosta, Osvaldo / Juárez-Cedillo, Teresa

PloS one

2021 Volume 16, Issue 11, Page(s) e0258414

Abstract: Background/aim: Medication prescription is a fundamental component in the care of the elderly. Several characteristics of aging and geriatric medicine affect prescriptions for these people and make the selection of drug therapy a difficult and complex ... ...

Abstract	Background/aim: Medication prescription is a fundamental component in the care of the elderly. Several characteristics of aging and geriatric medicine affect prescriptions for these people and make the selection of drug therapy a difficult and complex process. The objective of this study is to develop a geriatric portal for asynchronous online counseling (AGAlink) for use by physicians specializing in family medicine to reduce medication problems among older adult patients in the first level of care. Method: A qualitative study was carried out in the first level of care at the Mexican Institute of Social Security (IMSS), 31 family doctors were interviewed to identify attitudes, preferences about the use of the AGAlink geriatric portal, as well as their recommendations for the implementation of this tool in their daily practice. For the analysis of the data obtained, a qualitative thematic content analysis was used. Results: 90% of the physicians used the geriatric portal outside office hours without the need for the patient to be present. The perception of the physician towards the use of the AGAlink geriatric portal was favorable, provided relevant information and had several positive effects on the process of care for medical prescription. The barriers identified to accept the change in medication were not having the proposed therapeutic option, lack of any laboratory analysis, continuing to consider their experience for the prescription of the medication. Conclusions: The AGAlink geriatric portal was a tool that was well received by physicians who expressed a positive attitude, considered an investment of a short time that allowed them to update and learn about strategies to reduce the prescription problems presented among the elderly population. However, the main barrier was the use of technology, especially in the doctors with more seniority in the service.
MeSH term(s)	Adult ; Aged ; Counseling ; Female ; Geriatrics ; Health Planning Guidelines ; Humans ; Inappropriate Prescribing ; Internet ; Male ; Primary Health Care ; Surveys and Questionnaires
Language	English
Publishing date	2021-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0258414
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Article ; Online: Influence of COMT polymorphism in cognitive performance on dementia in community-dwelling elderly Mexican (SADEM study).

Juárez-Cedillo, Teresa / González-Figueroa, Evangelina / Martínez-Rodríguez, Nancy / Fragosos, Jose M / Garrido-Acosta, Osvaldo / Vargas-Alarcón, Gilberto

Metabolic brain disease

2021 Volume 36, Issue 6, Page(s) 1223–1229

Abstract: There is an inconsistent finding about the relationship of catechol-O-methyltransferase (COMT) with dementia susceptibility, as well as with cognitive impairment. To substantiate this, we examined COMT genotype effects in certain cognitive domains in ... ...

Abstract	There is an inconsistent finding about the relationship of catechol-O-methyltransferase (COMT) with dementia susceptibility, as well as with cognitive impairment. To substantiate this, we examined COMT genotype effects in certain cognitive domains in dementia. To evaluate the effects of COMT Val158Met on cognitive performance, we used The Mini-Mental State Examination (MMSE), the cognitive subscale of the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) and the Syndrome Kurz Test (SKT). The results show COMT Val/Met, Val/Val genotype polymorphisms had a significant effect on cognition performance (OR = 1.75 (95 %CI 1.22-2.54) and (OR = 2.76 (95 %CI 1.78-4.26), p < 0.001), and with adjustment for all cognitive test scores together, Val/Val (OR = 4.98 (95 % CI 1.47-16.86) and Val/Met (OR = 3.62 (95 % CI 1.37-9.56) had effect. Our study allows us to understand the role of COMT in cognitive performance in dementia, as well as interaction with other known risk factors for this pathology. This data might help in developing new therapeutic targets for cognitive impairment, main symptom of dementia. Other risk genotypes or haplotypes should be evaluated to determine the association with cognitive decline in dementia.
MeSH term(s)	Aged ; Aged, 80 and over ; Catechol O-Methyltransferase/genetics ; Cognition/physiology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/genetics ; Dementia/genetics ; Female ; Genotype ; Humans ; Male ; Mexican Americans ; Middle Aged ; Neuropsychological Tests ; Risk Factors
Chemical Substances	COMT protein, human (EC 2.1.1.6) ; Catechol O-Methyltransferase (EC 2.1.1.6)
Language	English
Publishing date	2021-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632824-6
ISSN	1573-7365 ; 0885-7490
ISSN (online)	1573-7365
ISSN	0885-7490
DOI	10.1007/s11011-021-00740-5
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Article ; Online: Tetracycline Derivatives Inhibit Plasmodial Cysteine Protease Falcipain-2 through Binding to a Distal Allosteric Site.

Hernández González, Jorge Enrique / Alberca, Lucas N / Masforrol González, Yordanka / Reyes Acosta, Osvaldo / Talevi, Alan / Salas-Sarduy, Emir

Journal of chemical information and modeling

2021 Volume 62, Issue 1, Page(s) 159–175

Abstract: Allosteric inhibitors regulate enzyme activity from remote and usually specific pockets. As they promise an avenue for less toxic and safer drugs, the identification and characterization of allosteric inhibitors has gained great academic and biomedical ... ...

Abstract	Allosteric inhibitors regulate enzyme activity from remote and usually specific pockets. As they promise an avenue for less toxic and safer drugs, the identification and characterization of allosteric inhibitors has gained great academic and biomedical interest in recent years. Research on falcipain-2 (FP-2), the major papain-like cysteine hemoglobinase of
MeSH term(s)	Allosteric Site ; Antimalarials/pharmacology ; Cysteine Endopeptidases ; Cysteine Proteases ; Cysteine Proteinase Inhibitors/chemistry ; Cysteine Proteinase Inhibitors/pharmacology ; Humans ; Kinetics ; Plasmodium falciparum ; Tetracyclines/pharmacology
Chemical Substances	Antimalarials ; Cysteine Proteinase Inhibitors ; Tetracyclines ; Cysteine Proteases (EC 3.4.-) ; Cysteine Endopeptidases (EC 3.4.22.-) ; falcipain 2 (EC 3.4.22.-)
Language	English
Publishing date	2021-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.1c01189
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Article ; Online: Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats.

Berlanga-Acosta, Jorge / Fernández-Mayola, Maday / Mendoza-Marí, Yssel / García-Ojalvo, Ariana / Martinez-Jimenez, Indira / Rodriguez-Rodriguez, Nadia / Playford, Raymond J / Reyes-Acosta, Osvaldo / Lopez-Marín, Laura / Guillén-Nieto, Gerardo

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. ... ...

Abstract	Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats' full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor's vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these "vascular disease drivers" may pave novel research avenues for atherosclerosis pathobiology.
MeSH term(s)	Aged ; Animals ; Arteriosclerosis/metabolism ; Arteriosclerosis/pathology ; Disease Models, Animal ; Female ; Granulation Tissue/metabolism ; Humans ; Male ; Middle Aged ; Popliteal Artery/injuries ; Proteins/administration & dosage ; Rats ; Vascular System Injuries/chemically induced ; Vascular System Injuries/pathology
Chemical Substances	Proteins
Language	English
Publishing date	2022-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031511
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Article: Development and validation of a questionnaire to evaluate satisfaction of the patient with diabetes at the primary care level.

Maldonado-Paredes, Sarahi Estrella / Juárez-Cedillo, Teresa / de la Peña, Jorge Escobedo / Vaca-Marín, Miguel Angel / Quiñones-Villalobos, Carolina / Garrido-Acosta, Osvaldo / González-Meléndez, Roberto C

Journal of family medicine and primary care

2022 Volume 11, Issue 5, Page(s) 2073–2082

Abstract: Aims: To develop and validate a new instrument to measure satisfaction with integral care (doctor-nurse) of the patient with type 2 diabetes mellitus, considering expectations-experiences together for the primary level of care.: Methods: The ... ...

Abstract	Aims: To develop and validate a new instrument to measure satisfaction with integral care (doctor-nurse) of the patient with type 2 diabetes mellitus, considering expectations-experiences together for the primary level of care. Methods: The instrument was constructed with questions regarding integral care to measure the satisfaction of the diabetes patient and was classified into four domains. The validity of the content was done through a panel of experts, apparent validity through a focus group, the validity of the construct through analysis of the main components and confirmatory factorial analysis, instrument reliability with internal consistency, determined by Cronbach alpha and temporal stability (test-retest). Results: The reliability of the questionnaire was 0.942. The intraclass correlation coefficient was 0.849. Validity of the construct showed acceptable goodness-of-fit and factorial structure with four factors: communication, empathy, technical care, care continuity, and 24 items for each domain, giving a Kayser-Meyer-Olkin index above 0.80 and a total variance above 73. Conclusions: The instrument is reliable and is also valid in terms of up into construct and content to evaluate satisfaction. Practice implications: In addition, these results allow to have elements for the design of strategies aimed at improving the relationship of health personnel with the patient.
Language	English
Publishing date	2022-05-14
Publishing country	India
Document type	Journal Article
ZDB-ID	2735275-4
ISSN	2278-7135 ; 2249-4863
ISSN (online)	2278-7135
ISSN	2249-4863
DOI	10.4103/jfmpc.jfmpc_2049_21
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Article ; Online: Relationship Between Genetic Variants of ACAT1 and APOE with the Susceptibility to Dementia (SADEM Study).

Alavez-Rubio, Jessica Sarahi / Martínez-Rodríguez, Nancy / Escobedo-de-la-Peña, Jorge / Garrido-Acosta, Osvaldo / Juárez-Cedillo, Teresa

Molecular neurobiology

2020 Volume 58, Issue 3, Page(s) 905–912

Abstract: One of the hypotheses that have emerged to explain the origin of dementia relates the disease with altered lipid metabolism, particularly cholesterol. To maintain cholesterol homeostasis, the ACAT1 enzyme has an important function to regulate the ... ...

Abstract	One of the hypotheses that have emerged to explain the origin of dementia relates the disease with altered lipid metabolism, particularly cholesterol. To maintain cholesterol homeostasis, the ACAT1 enzyme has an important function to regulate the production of Aβ. Moreover, APOE is the main cholesterol carrier in the brain, and it has been reported as a risk factor for this disease. This study evaluates the relationship between ACAT1 and APOE genetic variants with susceptibility for the development of Alzheimer's disease and other dementias. We examined four ACAT1 polymorphisms (rs2247071, rs2862616, rs3753526, rs1044925) and two in the APOE gene (rs7412, rs429358) in a group of 204 controls and 196 cases of dementia. Our results show one protective haplotype: CGCA (OR = 0.34, 95% CI = 0.23-0.46; p < 0.001) and one risk haplotype: CGGA (OR = 1.87, 95% CI = 1.34-2.60; p < 0.001) for the development of dementia. Subjects identified as APOE-ε4 allele carriers had a higher risk of developing dementia compared with non-carriers, OR = 13.33 (95% CI = 3.14-56.31). The results support the hypothesis that the ACAT1 gene, together with the APOE gene, plays an important role in susceptibility to the development of dementia and shows genetic characteristics of the Mexican population that can be used to identify the population at risk.
MeSH term(s)	Aged ; Aged, 80 and over ; Apolipoproteins E/genetics ; Case-Control Studies ; Dementia/genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Haplotypes/genetics ; Heterozygote ; Humans ; Linkage Disequilibrium/genetics ; Male ; Polymorphism, Genetic ; Sterol O-Acyltransferase/genetics
Chemical Substances	Apolipoproteins E ; Sterol O-Acyltransferase (EC 2.3.1.26) ; sterol O-acyltransferase 1 (EC 2.3.1.26)
Language	English
Publishing date	2020-10-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-020-02162-3
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Article ; Online: d-Amino acid substitutions and dimerization increase the biological activity and stability of an IL-15 antagonist peptide.

Rodríguez-Álvarez, Yunier / Cabrales-Rico, Ania / Diago-Abreu, David / Correa-Arguelles, Elianys / Reyes-Acosta, Osvaldo / Puente-Pérez, Pedro / Pichardo-Díaz, Dagmara / Urquiza-Noa, Dioslaida / Hernández-Santana, Amalia / Garay-Pérez, Hilda E

Journal of peptide science : an official publication of the European Peptide Society

2020 Volume 27, Issue 3, Page(s) e3293

Abstract: Interleukin (IL)-15 plays an important role in several inflammatory diseases. We have previously identified an IL-15 antagonist called P8 peptide, which binds specifically to IL-15 receptor alpha subunit. However, the P8 peptide rapidly degraded by ... ...

Abstract	Interleukin (IL)-15 plays an important role in several inflammatory diseases. We have previously identified an IL-15 antagonist called P8 peptide, which binds specifically to IL-15 receptor alpha subunit. However, the P8 peptide rapidly degraded by proteases, limiting its therapeutic application. Thus, we replaced each P8 peptide l-amino acid by its corresponding d-isomers. First, we determined the biological activity of the resulting peptides in a proliferation assay by using CTLL-2 cells. The substitution of l-Ala by d-Ala ([A4a]P8 peptide) increased the inhibitory effect of the P8 peptide in CTLL-2 cells in five-fold. In addition to that, the [A4a]P8 peptide dimer showed the most inhibitory effect. To protect the [A4a]P8 peptide and its dimer against exopeptidase activity, we acetylated the N-terminal of these peptides. At least a three-fold reduction in antagonist activity of acetylated peptides was exhibited. However, the substitution of the N-terminal l-Lys residue of [A4a]P8 peptide and its dimer by d-Lys ([K1k;A4a]P8 peptide) did not affect the antagonist effect of the aforementioned peptides. The [K1k;A4a]P8 peptide dimer was stable to the degradation of trypsin, chymotrypsin, and pepsin up until 48 min. Also, the safety and immunogenicity studies in healthy BALB/c mice demonstrated that the administration of this peptide did not affect the clinical parameters of the animals nor generated antipeptide antibodies. Our findings reveal that two distinct d-amino acid substitutions and dimerization increase the biological activity and stability of P8 peptide. The resulting peptide constitutes a novel IL-15 antagonist with potential applicability in inflammatory diseases.
MeSH term(s)	Amino Acid Substitution/drug effects ; Animals ; Cell Line ; Cell Proliferation/drug effects ; Dimerization ; Female ; Interleukin-15/antagonists & inhibitors ; Interleukin-15/metabolism ; Mice ; Mice, Inbred BALB C ; Peptides/chemical synthesis ; Peptides/chemistry ; Peptides/pharmacology
Chemical Substances	Interleukin-15 ; Peptides
Language	English
Publishing date	2020-12-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1234416-3
ISSN	1099-1387 ; 1075-2617
ISSN (online)	1099-1387
ISSN	1075-2617
DOI	10.1002/psc.3293
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Article: Adaptation of Lorke's method to determine and compare ED50 values: The cases of two anticonvulsants drugs

Garrido-Acosta, Osvaldo / Meza-Toledo, Sergio Enrique / Anguiano-Robledo, Liliana / Valencia-Hernández, Ignacio / Chamorro-Cevallos, Germán

Journal of pharmacological and toxicological methods. 2014 July, Aug., v. 70, no. 1

2014

Abstract: We determined the median effective dose (ED₅₀) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice ... ...

Abstract	We determined the median effective dose (ED₅₀) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice per compound tested.The anticonvulsant activities of phenobarbital and sodium valproate were evaluated in male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of pentylenetetrazole (PTZ). The anticonvulsant ED₅₀ values were obtained through modifications of Lorke's method that involved changes in the selection of the three first doses in the initial test and the fourth dose in the second test. Furthermore, a test was added to evaluate the ED₅₀ calculated by the modified Lorke's method, allowing statistical analysis of the data and determination of the confidence limits for ED₅₀.The ED₅₀ for phenobarbital against MES- and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium valproate values were 261.2mg/kg and 159.7mg/kg, respectively.These results are similar to those found using the traditional methods of finding ED₅₀, suggesting that the modifications made to Lorke's method generate equal results using fewer mice while increasing confidence in the statistical analysis. This adaptation of Lorke's method can be used to determine median letal dose (LD₅₀) or ED₅₀ for compounds with other pharmacological activities.
Keywords	intraperitoneal injection ; males ; phenobarbital ; sodium ; statistical analysis ; toxicology
Language	English
Dates of publication	2014-07
Size	p. 66-69.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2014.05.002
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Article ; Online: In vitro and in vivo characterization of an interleukin-15 antagonist peptide by metabolic stability,

Rodríguez-Álvarez, Yunier / Cabrales-Rico, Ania / Perera-Pintado, Alejandro / Prats-Capote, Anais / Garay-Pérez, Hilda E / Reyes-Acosta, Osvaldo / Pérez-García, Erik / Chico-Capote, Araceli / Santos-Savio, Alicia

Journal of peptide science : an official publication of the European Peptide Society

2018 Volume 24, Issue 4-5, Page(s) e3078

Abstract: Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with potential ... ...

Abstract	Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with
MeSH term(s)	Animals ; Arthritis, Rheumatoid/blood ; Cell Line ; Humans ; In Vitro Techniques ; Interleukin-15/antagonists & inhibitors ; Mice ; Peptides/chemical synthesis ; Peptides/chemistry ; Peptides/pharmacokinetics ; Protein Stability ; Rats ; Rats, Wistar ; Synovial Fluid/chemistry ; Technetium/chemistry ; Tissue Distribution
Chemical Substances	Interleukin-15 ; Peptides ; Technetium (7440-26-8)
Language	English
Publishing date	2018-04-15
Publishing country	England
Document type	Journal Article
ZDB-ID	1234416-3
ISSN	1099-1387 ; 1075-2617
ISSN (online)	1099-1387
ISSN	1075-2617
DOI	10.1002/psc.3078
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