Artículos (Bioquímica Médica y Biología Molecular e Inmunología)

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Differences of the 6N and 6J Substrains of C57BL/6 Mice inthe Development of Experimental AutoimmuneEncephalomyelitis
(Wiley, 2025-07-02) Alvarez Lopez, Ana Isabel; Ponce-España E.; Cruz Chamorro, Ivan; Santos Sanchez, Guillermo; Bejarano Hernando, Ignacio; Alvarez Sanchez, Nuria; Lardone, Patricia Judith; Carrillo Vico, Antonio; Bioquímica Médica y Biología Molecular e Inmunología; Junta de Andalucía; Gobierno de España; CTS160: Neuroinmunoendocrinología Molecular
Multiple sclerosis (MS) is an autoimmune disease causing neuroinflammation and demyelination in the central nervous system (CNS). It is traditionally considered CD4+ T cell-mediated, but several immune cells, such as CD8+ cells, B cells, macrophages, and dendritic cells (DC) also contribute to the pathogenesis. Moreover, altered gut microbiota, including changes in specific genera, has been observed in MS patients. The murine model of MS, experimental autoimmune encephalomyelitis (EAE), is mainly carried out in C57BL/6 mice. Historically, N and J substrains have been used interchangeably, and many laboratories are not even aware of which strain they are using. Therefore, the objective of this study was to evaluate the differences between the 6J and 6N substrains subjected to myelin oligodendrocyte glycoprotein (MOG35–55) induced EAE in the composition of neuroinflammatory cells and microbiota. 6J substrain presented a more severe EAE than the 6N substrain, accompanied by an increase in the frequency of macrophages, CD8+, and B cells within the infiltrated immune cells compartment. In addition, 6J animals have a higher proinflammatory profile and a lower anti-inflammatory profile compared with the 6N substrain. Consistent with this, the differences observed in the basal microbial taxa between both substrains support the differences observed in the immunological response.
MPXV and SARS-CoV-2 in the air of nightclubs in Spain
(Elsevier, 2024-03-24) Sanchiz, África; Martín, Rocío; Val, Margarita del; Corell-Almuzara, Alfredo; Alcamí, Antonio; Bioquímica Médica y Biología Molecular e Inmunología; Consejo Superior de Investigaciones Cientficas (PTI Salud Global)
MOMAST((R)) Reduces the Plasmatic Lipid Profile and Oxidative Stress and Regulates Cholesterol Metabolism in a Hypercholesterolemic Mouse Model: The Proof of Concept of a Sustainable and Innovative Antioxidant and Hypocholesterolemic Ingredient
(MDPI, 2023-06-24) Cruz Chamorro, Iván; Santos-Sanchez, G; Ponce España, Eduardo; Bollati, Carlotta; d'Adduzio, Lorenza; Bartolomei, Martina; Carrillo Vico, Antonio; Lammi, Carmen; Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía Consejería de Economía, Conocimiento, Empresa y Universidad; Fundacion de Investigacion de la Universidad de Sevilla-FIUS; Ministerio de Educación, Cultura y Deporte de España; CTS160: Neuroinmunoendocrinología Molecular
MOMAST® is a patented natural phenolic complex, rich in tyrosol (9.0 g/kg, Tyr), hydroxityrosol (43,5 g/kg, OH-Tyr), and verbascoside (5.0 g/Kg), which is obtained from the OVW by-product of the Coratina cultivar with potent direct antioxidant activity (measured by DPPH and FRAP assays, respectively). Indeed, MOMAST® represents an innovative sustainable bioactive ingredient which has been obtained with ethical and empowering behavior by applying the principles of a circular economy. In the framework of research aimed at fostering its health-promoting activity, in this study it was clearly demonstrated that MOMAST® treatment reduced the oxidative stress and levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, and increased the HDL levels, without changes in the triglyceride (TG) levels in Western diet (WD)-fed mice. The modulation of the plasmatic lipid profile is similar to red yeast rice (RYR) containing Monacolin K (3%). In addition, at the molecular level in liver homogenates, similarly to RYR, MOMAST® exerts cholesterol-lowering activity through the activation of LDL receptor, whereas, unlike RYR, MOMAST® reduces proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels via hepatic nuclear factor 1 (HNF1)-α activation. Hence, this study provides the proof of concept regarding the hypocholesterolemic activity of MOMAST, which could be successfully exploited as an active ingredient for the development of innovative and sustainable dietary supplements and functional foods.
Baseline resistance-guided therapy does not enhance the response to interferon-free treatment of HCV infection in real life
(Nature Publishing Group; Nature Portfolio, 2018-10-08) Real Navarrete, Luis Miguel; Macías Sánchez, Juan; Pérez, Ana B.; Merino, Dolores; Granados, Rafael; Morano, Luis; Ríos-Villegas, María José; Merchante Gutiérrez, Nicolás; Pineda Vergara, Juan Antonio; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Universidad de Sevilla. TIC154: Departamento de Ingeniería Telemática
Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be influenced by the presence of resistance-associated substitutions (RASs). This study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of sustained viral response (SVR) in naïve HCV-infected patients in clinical practice. All HCV-infected patients who initiated treatment with interferon (IFN)-free DAA based regimens between March 2016 and May 2017 in 17 Spanish hospitals and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were included. Patients had to be DAA naïve, with the exception of sofosbuvir with/without IFN. In one hospital, participants received therapy guided by the presence of NS5A-RASs (RGT population). Patients enrolled in the remaining hospitals, without baseline RASs testing, constituted the control population. A total of 120 and 512 patients were included in the RGT and control populations, respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A-RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2% (three relapses) whereas it was 98.8% (six relapses) in the control population (p = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naïve HCV-infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy in clinical practice.
Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles ¿Qué parámetros debe incluir un perfil lipídico básico?
(Ediciones doyma S A; Idepsa; Elsevier BV, 2023) Arrobas Velilla, Teresa; Guijarro Herráiz, Carlos; Campuzano Ruiz, Raquel; Rodríguez-Piñero, Manuel; Valderrama Marcos, José Francisco; Pérez Pérez, Antonio; Botana López, Antonio M.; Castilla Guerra, Luis; Salgueira Lazo, Mercedes; Bruño Soto, Antonio; Multidisciplinary task force for lipids and vascular risk; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. CTS151: Bioquímica Medica
Las enfermedades cardiovasculares (ECV) siguen siendo la principal causa de muerte en nuestro país. El control adecuado de las alteraciones del metabolismo lipídico es un reto clave en prevención cardiovascular que está lejos de alcanzarse en la práctica clínica real. Existe una gran heterogeneidad en los informes del metabolismo lipídico de los laboratorios clínicos espa˜noles, lo que puede contribuir al mal control del mismo. Por ello, un grupo de trabajo de las principales sociedades científicas implicadas en la atención de los pacientes de riesgo vascular hemos elaborado este documento con una propuesta básica de consenso sobre la determinación del perfil lipídico básico en prevención cardiovascular, recomendaciones para su realización y unificación de criterios para incorporar los objetivos de control lipídico adecuados al riesgo vascular de los pacientes en los informes de laboratorio.
Co-15. Dieta mediterránea suplementada con aceite de oliva virgen extra. Estudio aleatorizado para evaluar el impacto en la ehgna
(Aula Médica, 2023) Del Pino Bellido, P.; Rodriguez Delgado, C.; Vías Parrado, C.; Cordero Ruiz, Patricia; Bellido Muñoz, F.; Valladolid León, J.M.; Caunedo Álvarez, Ángel; Sánchez Margalet, Víctor; Jimenez Cortegana, Carlos; Carmona-Soria, Isabel; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. CTS151: Bioquímica Medica
La inflamación del tejido adiposo y el estrés oxidativo se han relacionado con la progresión de la enfermedad hepática grasa no alcohólica (EHGNA). En situaciones de inflamación crónica se ha descrito una acumulación de células mieloides inmaduras con función inmunosupresora (MDSC). Aunque se ha descrito su papel en neoplasias, también se ha sugerido que el número de MDSC se relaciona con la fibrosis y la inflamación hepática. La intervención dietética es el único tratamiento eficaz en la EHGNA. El aceite de oliva virgen extra (AOVE) parece tener un papel “protector”, puesto que parece reducir la resistencia a la insulina y favorecer la regulación a la baja de los genes lipogénicos.
Health properties of plant bioactive compounds: immune, antioxidant, and metabolic effects
(MDPI, 2023-04-26) Cruz Chamorro, Ivan; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejeria de Salud y Familias; Ministerio de Economía, Industria y Competitividad; Junta de Andalucía; Universidad de Sevilla. CTS160: Neuroinmunoendocrinología Molecular
In recent decades, people in the industrialized world have increased the demand for meat-free foods motivated by health, environmental, and animal welfare reasons [...].
Incidence of and factor sassociated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic
(Wiley, 2021-08-17) Fernández-Fuertes, Marta; Corma-Gómez, Anaís;; Torres, Eva; Rodríguez-Pineda, Elena; Fuentes-López, Ana; Rincón, Pilar; Fernández, Nieves; García, Federico; Bernal, Samuel; Real Navarrete, Luis Miguel; Macías Sánchez, Juan; Pineda Vergara, Juan Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Medicina; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Gobierno de España
Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%–9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%–9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%–2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16–0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
(Natural Academy Sciences, 2023-08-29) Le Guen, Yann; Luo, Guo; Ambati, Aditya; Damotte, Vincent; Jansen, Iris E.; Yu, Eric; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Swieten, John Van; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
We report that specific HLA-DRB1*04 alleles are protective against Alzheimer’s dementia (AD), Parkinson’s disease (PD), and other neurodegenerative disorders. Further, we found that these HLA (Human Leukocyte Antigen) subtypes selectively bind a piece of Tau crucial to aggregation but only when it is acetylated (a-PHF6). This a-PHF6 piece is significant as it is a common posttranslational modification of Tau found in Alzheimer’s brains. Only when someone is HLA-DRB1*04:04 or HLA-DRB1*04:01 can PHF6 be presented as a T cell epitope to T cell receptors and mount a memory immune response against this pro-aggregation fragment. This immune response would protect against AD, PD, and neurodegeneration, explaining the HLA association. Vaccination with a-PHF6 in HLA-DRB1*04 individuals could have preventive effects.
Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk
(BMC (BioMed Central), 2023-11-17) Martín-Escolano, Rubén; Vidal-Alcántara, Erick Joan; Crespo, Javier; Ryan, Pablo; Real Navarrete, Luis Miguel; Lazo-Álvarez, Juan Ignacio; Fernández-Rodríguez, Amanda; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS)
Background About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infec tion (SC group) and individuals without evidence of HCV infection (C group). Methods We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log link) adjusted by significant variables and sex. Results 13 ICs (BTLA, CD137(4 1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG 3, PD 1, PD L1, PD L2, and TIM 3) and 13 SASP proteins (EGF, Eotaxin, IL 1alpha, IL 1RA, IL 8, IL 13, IL 18, IP 10, SDF 1alpha, HGF, beta NGF, PLGF 1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After strati fying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD L2 was significantly higher in SC women, and no differences in SASP were found. Conclusions Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non hepatic diseases.
Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: what parameters should a basic lipid profile include?
(De Gruyter Brill, 2023-06-05) Arrobas Velilla, Teresa; Guijarro, Carlos; Campuzano Ruiz, Raquel; Rodríguez Piñero, Manuel; Valderrama Marcos, José Francisco; Pérez Pérez, Antonio; Botana López, Antonio M.; Castilla Guerra, Luis; Salgueira Lazo, Mercedes; Autoría grupal: Multidisciplinary task force for lipids and vascular risk; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. CTS151: Bioquímica Medica
Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.
Homocysteine and C-reactive protein levels are associated with frailty in older spaniards: the Toledo study for healthy aging
(Oxford University Press, 2019-07-13) Álvarez-Sánchez, Nuria; Álvarez-Ríos, Ana Isabel; Guerrero Montávez, Juan Miguel; García-García, Francisco J.; Rodríguez-Mañas, Leocadio; Cruz Chamorro, Iván; Lardone, Patricia Judith; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejería de Salud, Junta de Andalucía; Instituto de Salud Carlos III (Ministerio de Ciencia e Innovación); Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad); Junta de Andalucía; Ministerio de Educación, Cultura y Deporte (MECD). España; Universidad de Sevilla. CTS160: Neuroinmunoendocrinología Molecular
High-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) are inflammation markers but are also related to cardiovascular diseases, disability, or higher risk of death. Although inflammation is considered to be associated with frailty, data regarding the association between hsCRP or Hcy and frailty are controversial or scarce, especially with respect to their association with prefrailty. Thus, our objective was to study the association of hsCRP and Hcy with prefrailty and frailty in 1,211 Spanish men and women aged 65–98 years from the Toledo Study for Healthy Aging (TSHA) cohort, classified according to Fried’s criteria. Hcy was independently associated with frailty (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.01–1.12), whereas hsCRP was independently associated with both prefrailty (OR = 1.03; 95% CI: 1.01–1.06) and frailty (OR = 1.07; 95% CI: 1.02–1.12). Furthermore, both markers were positively correlated with the number of Fried’s criteria that were met and were independently associated with the criteria of exhaustion (Hcy: OR = 1.03, 95% CI: 1.00–1.06), weakness (hsCRP: OR = 1.03, 95% CI: 1.01–1.05), and low physical activity (hsCRP: OR = 1.04, 95% CI: 1.02–1.06). Thus, our results highlight the importance of inflammation in age-related physical decline and, in particular, its association with fatigue, low strength, and decreased physical activity.
Author Correction: Common variants in Alzheimer's disease and risk stratification by polygenic risk scores
(Nature publishing group, 2023-02-02) de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, IE; Real Navarrete, Luis Miguel; Mir Rivera, Pablo; Ruiz, A; Eadb Contributors; GRACE Study Group; Degesco Consortium; IGAP (ADGC, CHARGE, EADI, GERAD); PGC-ALZ consortia; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Author Correction.
Maternal separation differentially modulates early pathology by sex in 5xFAD Alzheimer's disease-transgenic mice
(Elsevier, 2023-10) Garcia, M. G.; Paulus, A.; Vázquez-Reyes, S.; Klementieva, O.; Gouras, G. K.; Bachiller, Sara; Deierborg, T.; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
Alzheimer's disease (AD) is the most common neurodegenerative disease. Most cases of AD are considered idiopathic and likely due to a combination of genetic, environmental, and lifestyle-related risk factors. Despite occurring decades before the typical age of an AD diagnosis, early-life stress (ELS) has been suggested to have long-lasting effects that may contribute to AD risk and pathogenesis. Still, the mechanisms that underlie the role of ELS on AD risk remain largely unknown. Here, we used 5xFAD transgenic mice to study relatively short-term alterations related to ELS in an AD-like susceptible mouse model at 6 weeks of age. To model ELS, we separated pups from their dams for 3 h per day from postnatal day 2-14. Around 6 weeks of age, we found that maternally separated (MS) 5xFAD mice, particularly female mice, displayed increased amyloid-β-immunoreactivity in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). In anterior cingulate cortex, we also noted significantly increased intraneuronal amyloid-β-immunoreactivity associated with MS but only in female mice. Moreover, IBA1-positive DAPI density was significantly increased in relation to MS in ACC and BLA, and microglia in BLA of MS mice had significantly different morphology compared to microglia in non-MS 5xFAD mice. Cytokine analysis showed that male MS mice, specifically, had increased levels of neuroinflammatory markers CXCL1 and IL-10 in hippocampal extracts compared to non-MS counterparts. Additionally, hippocampal extracts from both male and female MS 5xFAD mice had decreased levels of synapse- and activity-related markers Bdnf, 5htr6, Cox2, and Syp in hippocampus. Lastly, we performed behavioral tests to evaluate anxiety- and depressive-like behavior and working memory but could not detect any significant differences between groups. Overall, we detected several sex-specific molecular and cellular alterations in 6-week-old adolescent 5xFAD mice associated with MS that may help explain the connection between ELS and AD risk.
Chemical and biological characterization of the DPP-IV inhibitory activity exerted by lupin (Lupinus angustifolius) peptides: From the bench to the bedside investigation
(Elsevier, 2023-06-02) Cruz Chamorro, Ivan; Santos Sanchez, Guillermo; Bollati, Carlotta; Bartolomei, Martina; Capriotti, Anna Laura; Cerrato, Andrea; Millan Linares, Carmen; Lagana, Aldo; Carrillo Vico, Antonio; Lammi, Carmen; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejeria de Salud; Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades, Junta de Andalucia; Ministerio de Educacion, Cultura y Deporte, Gobierno de España; Ministerio de Economía y Competitividad, Gobierno de España; PAIDI Program from Junta de Andalucia; Universidad de Sevilla; Universidad de Sevilla. CTS160: Neuroinmunoendocrinología Molecular
Dipeptidyl peptidase IV (DPP-IV) is considered a key target for the diabetes treatment, since it is involved in glucose metabolism. Although lupin protein consumption shown hypoglycemic activity, there is no evidence of its effect on DPP-IV activity. This study demonstrates that a lupin protein hydrolysate (LPH), obtained by hydrolysis with Alcalase, exerts anti-diabetic activity by modulating DPP-IV activity. In fact, LPH decreased DPP-IV activity in a cell-free and cell-based system. Contextually, Caco-2 cells were employed to identify LPH peptides that can be intestinally trans-epithelial transported. Notably, 141 different intestinally transported LPH sequences were identified using nano- and ultra-chromatography coupled to mass spectrometry. Hence, it was demonstrated that LPH modulated the glycemic response and the glucose concentration in mice, by inhibiting the DPP-IV. Finally, a beverage containing 1 g of LPH decreased DPP-IV activity and glucose levels in humans.
X-chromosome-wide association study for Alzheimer's disease
(Nature publishing group; Springernature; Springer Science and Business Media LLC, 2024-12-04) Le Borgne, Julie; Heikkinen, Sami; Amin, Najaf; Ahmad, Shahzad; Choi, Seung Hoan; Bis, Joshua; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Rodriguez-Rodriguez, Eloy; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); NIA NIH HHS
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.
The immune system in Parkinson's disease: what we know so far
(Oxford UNIV PRESS, 2024-09-17) Roodveldt, Cintia; Bernardino, Liliana; Oztop-Cakmak, Ozgur; Dragic, Milorad; Fladmark, Kari Espolin; Ertan, Sibel; Busra, Aktas; Romero-Ramos, Marina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Agencia Nacional de Investigación y Desarrollo de Chile (ANID); COST (Cooperación Europea en Ciencia y Tecnología); Unión Europea; Fundación para la Ciencia y la Tecnología; Ministerio de Universidades (Ministerio de Universidades de España); Instituto Nacional de Investigación en Salud y Atención (NIHR) Centro de Investigación Biomédica de Cambridge; Ministerio de Ciencia e Innovación de España; Universidad de Sevilla. CTS677: Terapias Avanzadas en Inmunomodulación y Neuroprotección
Parkinson's disease is characterized neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses mediated by microglia and astrocytes, which may be elicited by pathological α-syn or signals from affected neurons and other cell types, and are directly linked to neurodegeneration and disease development. Apart from the prominent immune alterations seen in the CNS, including the infiltration of T cells into the brain, more recent studies have demonstrated important changes in the peripheral immune profile within both the innate and adaptive compartments, particularly involving monocytes, CD4+ and CD8+ T cells. This review aims to integrate the consolidated understanding of immune-related processes underlying the pathogenesis of Parkinson's disease, focusing on both central and peripheral immune cells, neuron-glia crosstalk as well as the central-peripheral immune interaction during the development of Parkinson's disease. Our analysis seeks to provide a comprehensive view of the emerging knowledge of the mechanisms of immunity in Parkinson's disease and the implications of this for better understanding the overall pathogenesis of this disease.
Role of Nutrients Regulating Myeloid Derived Suppressor Cells in Cancer: A Scoping Review
(MDPI, 2024-08-23) Pérez-Peláez, Beatriz; Jimenez Cortegana, Carlos; Cruz Merino, Luis de la; Sánchez Margalet, Víctor; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS151: Bioquímica Medica
Myeloid-derived suppressor cells (MDSCs) are immature cells with an immunosuppressive function. MDSCs have been related to inflammation in many settings, including infections, transplantation, obesity, aging, or cancer. In oncological settings, MDSCs participate in tumor immunoescape, growth, and metastasis. Certain nutrients can modify chronic inflammation by their interaction with MDSCs. Therefore, the possible influence of certain nutrients on immune surveillance by their actions on MDSCs and how this may affect the prognosis of cancer patients were evaluated in this scoping review. We identified seven papers, six of which were murine model studies and only one was a human clinical trial. Globally, a significant reduction in cancer growth and progression was observed after achieving a reduction in both MDSCs and their immunosuppressive ability with nutrients such as selected vegetables, icaritin, retinoic acid, curdlan, active vitamin D, soy isoflavones, and green tea. In conclusion, the consumption of certain nutrients may have effects on MDSCs, with beneficial results not only in the prevention of tumor development and growth but also in improving patients' response.
From ‘Farm to Fork’: Exploring the Potential of Nutrient-Rich and Stress-Resilient Emergent Crops for Sustainable and Healthy Food in the Mediterranean Region in the Face of Climate Change Challenges
(MDPI, 2024-07-11) Matías, Javier; Rodríguez, María José; Carrillo Vico, Antonio; Casals, Joan; Fondevilla, Sara; Haros, Claudia Mónika; Pedroche, Justo; Reguera, María; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Agencia Estatalde Investigación-Ministerio de Ciencia e Innovación (MICINN, España); Universidad de Sevilla. CTS160: Neuroinmunoendocrinología Molecular
In the dynamic landscape of agriculture and food science, incorporating emergent crops appears as a pioneering solution for diversifying agriculture, unlocking possibilities for sustainable cultivation and nutritional bolstering food security, and creating economic prospects amid evolving environmental and market conditions with positive impacts on human health. This review explores the potential of utilizing emergent crops in Mediterranean environments under current climate scenarios, emphasizing the manifold benefits of agricultural and food system diversification and assessing the impact of environmental factors on their quality and consumer health. Through a deep exploration of the resilience, nutritional value, and health impacts of neglected and underutilized species (NUS) such as quinoa, amaranth, chia, moringa, buckwheat, millet, teff, hemp, or desert truffles, their capacity to thrive in the changing Mediterranean climate is highlighted, offering novel opportunities for agriculture and functional food development. By analysing how promoting agricultural diversification can enhance food system adaptability to evolving environmental conditions, fostering sustainability and resilience, we discuss recent findings that underscore the main benefits and limitations of these crops from agricultural, food science, and health perspectives, all crucial for responsible and sustainable adoption. Thus, by using a sustainable and holistic approach, this revision analyses how the integration of NUS crops into Mediterranean agrifood systems can enhance agriculture resilience and food quality addressing environmental, nutritional, biomedical, economic, and cultural dimensions, thereby mitigating the risks associated with monoculture practices and bolstering local economies and livelihoods under new climate scenarios.
Role of leptin in obesity, cardiovascular disease, and type 2 diabetes
(MDPI, 2024-02-16) Vilariño-García, Teresa; Polonio-González, María L.; Pérez Pérez, Antonio; Ribalta, Josep; Arrieta, Francisco; Aguilar, Manuel; Obaya, Juan C.; Durán García, Santiago; Sánchez Margalet, Víctor; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía; Universidad de Sevilla. CTS151: Bioquímica Medica
Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90-95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as the primary cause of morbidity and mortality, placing a substantial burden on healthcare systems due to the potential for macrovascular and microvascular complications. In this context, leptin, an adipocyte-derived hormone, plays a fundamental role. This hormone is essential for regulating the cellular metabolism and energy balance, controlling inflammatory responses, and maintaining CV system homeostasis. Thus, leptin resistance not only contributes to weight gain but may also lead to increased cardiac inflammation, greater fibrosis, hypertension, and impairment of the cardiac metabolism. Understanding the relationship between leptin resistance and CV risk in obese individuals with type 2 DM (T2DM) could improve the management and prevention of this complication. Therefore, in this narrative review, we will discuss the evidence linking leptin with the presence, severity, and/or prognosis of obesity and T2DM regarding CV disease, aiming to shed light on the potential implications for better management and preventive strategies.

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