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1.
Emerg Microbes Infect ; 13(1): 2368202, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38970562

RESUMEN

Influenza A viruses (IAV) impose significant respiratory disease burdens in both swine and humans worldwide, with frequent human-to-swine transmission driving viral evolution in pigs and highlighting the risk at the animal-human interface. Therefore, a comprehensive One Health approach (interconnection among human, animal, and environmental health) is needed for IAV prevention, control, and response. Animal influenza genomic surveillance remains limited in many Latin American countries, including Colombia. To address this gap, we genetically characterized 170 swine specimens from Colombia (2011-2017). Whole genome sequencing revealed a predominance of pandemic-like H1N1 lineage, with a minority belonging to H3N2 and H1N2 human seasonal-like lineage and H1N1 early classical swine lineages. Significantly, we have identified reassortant and recombinant viruses (H3N2, H1N1) not previously reported in Colombia. This suggests a broad genotypic viral diversity, likely resulting from reassortment between classical endemic viruses and new introductions established in Colombia's swine population (e.g. the 2009 H1N1 pandemic). Our study highlights the importance of a One Health approach in disease control, particularly in an ecosystem where humans are a main source of IAV to swine populations, and emphasizes the need for continued surveillance and enhanced biosecurity measures. The co-circulation of multiple subtypes in regions with high swine density facilitates viral exchange, underscoring the importance of monitoring viral evolution to inform vaccine selection and public health policies locally and globally.


Asunto(s)
Evolución Molecular , Variación Genética , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Filogenia , Enfermedades de los Porcinos , Animales , Porcinos , Colombia/epidemiología , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/veterinaria , Infecciones por Orthomyxoviridae/epidemiología , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/epidemiología , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Salud Única , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/aislamiento & purificación , Secuenciación Completa del Genoma , Genoma Viral , Monitoreo Epidemiológico , Virus Reordenados/genética , Virus Reordenados/clasificación , Virus Reordenados/aislamiento & purificación , Subtipo H1N2 del Virus de la Influenza A/genética , Subtipo H1N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N2 del Virus de la Influenza A/clasificación , Gripe Humana/virología , Gripe Humana/epidemiología
2.
Viruses ; 16(6)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38932133

RESUMEN

Equine influenza is a viral disease caused by the equine influenza virus (EIV), and according to the WOAH, it is mandatory to report these infections. In Latin America and Colombia, EIV risk factors have not been analyzed. The objective of this research is to perform an epidemiological and molecular analysis of the EIV in horses with respiratory symptoms from 2020 to 2023 in Colombia. Molecular EIV detection was performed using RT-qPCR and nanopore sequencing. A risk analysis was also performed via the GEE method. A total of 188 equines with EIV respiratory symptoms were recruited. The positivity rate was 33.5%. The descriptive analysis showed that only 12.8% of the horses were vaccinated, and measures such as the quarantine and isolation of symptomatic animals accounted for 91.5% and 88.8%, respectively. The variables associated with the EIV were the non-isolation of positive individuals (OR = 8.16, 95% CI (1.52-43.67), p = 0.014) and sharing space with poultry (OR = 2.16, 95% CI (1.09-4.26), p = 0.027). In conclusion, this is the first EIV investigation in symptomatic horses in Colombia, highlighting the presence of the virus in the country and the need to improve preventive and control measures.


Asunto(s)
Enfermedades de los Caballos , Subtipo H3N8 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Caballos , Animales , Colombia/epidemiología , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/veterinaria , Infecciones por Orthomyxoviridae/virología , Enfermedades de los Caballos/virología , Enfermedades de los Caballos/epidemiología , Subtipo H3N8 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N8 del Virus de la Influenza A/genética , Femenino , Masculino , Filogenia , Secuenciación de Nanoporos/métodos , Factores de Riesgo
3.
Environ Res ; 255: 119179, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38768882

RESUMEN

Exposure to particulate matter (PM) pollution is a significant health risk, driving the search for innovative metrics that more accurately reflect the potential harm to human health. Among these, oxidative potential (OP) has emerged as a promising health-based metric, yet its application and relevance across different environments remain to be further explored. This study, set in two high-altitude Bolivian cities, aims to identify the most significant sources of PM-induced oxidation in the lungs and assess the utility of OP in assessing PM health impacts. Utilizing two distinct assays, OPDTT and OPDCFH, we measured the OP of PM samples, while also examining the associations between PM mass, OP, and black carbon (BC) concentrations with hospital visits for acute respiratory infections (ARI) and pneumonia over a range of exposure lags (0-2 weeks) using a Poisson regression model adjusted for meteorological conditions. The analysis also leveraged Positive Matrix Factorization (PMF) to link these health outcomes to specific PM sources, building on a prior source apportionment study utilizing the same dataset. Our findings highlight anthropogenic combustion, particularly from traffic and biomass burning, as the primary contributors to OP in these urban sites. Significant correlations were observed between both OPDTT and PM2.5 concentration exposure and ARI hospital visits, alongside a notable association with pneumonia cases and OPDTT levels. Furthermore, PMF analysis demonstrated a clear link between traffic-related pollution and increased hospital admissions for respiratory issues, affirming the health impact of these sources. These results underscore the potential of OPDTT as a valuable metric for assessing the health risks associated with acute PM exposure, showcasing its broader application in environmental health studies.


Asunto(s)
Contaminantes Atmosféricos , Altitud , Ciudades , Material Particulado , Material Particulado/análisis , Bolivia/epidemiología , Humanos , Contaminantes Atmosféricos/análisis , Adulto , Infecciones del Sistema Respiratorio/epidemiología , Oxidación-Reducción , Masculino , Persona de Mediana Edad , Femenino , Neumonía/epidemiología , Neumonía/inducido químicamente , Adulto Joven , Adolescente , Contaminación del Aire/análisis , Contaminación del Aire/efectos adversos , Niño , Monitoreo del Ambiente/métodos , Preescolar
4.
Front Pediatr ; 12: 1410850, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38803639

RESUMEN

Introduction: Acute appendicitis secondary to parasitic infections is uncommon, being detected in less than 1% of cases. Balantidium coli is a parasite found in pigs and primates with zoonotic potential. To date, only three cases of acute appendicitis induced by this parasite have been documented globally. Case: A 7-year-old female patient, who consumed pork daily, presented to the emergency department with a one-day history of abdominal pain in the lower quadrants, described as colic-like, alongside abdominal distension. Initial abdominal radiography led to a diagnosis of intestinal obstruction. Conservative management without therapeutic response necessitated referral to a higher complexity center. Upon admission, an abdominal computed tomography scan diagnosed acute appendicitis and secondary ileus. During surgical intervention, an appendiceal phlegmon formed by loops of the small intestine was mechanically released, revealing a perforated appendix with extensive fecal peritoneal contamination. Pathological analysis identified an inflammatory infiltrate and the presence of Balantidium coli trophozoites. Medical treatment included Piperacillin-Tazobactam and Metronidazole. The patient was discharged after 10 days of medical treatment. Discussion: Acute appendicitis caused by Balantidium coli is a rare occurrence. It is crucial to identify parasites in pathological samples due to their impact on postoperative management. The close contact between humans and pigs, especially in developing countries, suggests that the prevalence of parasitic infection and colonization by Balantidium coli may be higher than currently recognized. Regarding the identification of this patient's specific exposure, the regular consumption of pork suggests the hypothesis that improper processing is linked to the acquisition of the parasitic infection.

5.
Front Pediatr ; 12: 1350697, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38571702

RESUMEN

Introduction: Hepatoblastoma is the most common malignant primary liver tumor in the pediatric population, accounting for 67% of cases in the United States. Surgical resection is the only curative treatment option; however, it can be performed in only 10% of patients with primary tumors. The two most common limitations for resection are the need for extensive resections and tumors in central locations. The therapeutic hypertrophy of healthy tissue achieved with ALPPS (Associating Liver Partition and Portal vein ligation for Staged Hepatectomy) enables larger resections and has been successfully employed in the pediatric population in recent years. Objective: To present three cases of patients with centrally located PRETEXT II or III hepatoblastomas who underwent ALPPS procedure as a viable therapeutic alternative to liver transplantation. Discussion and results: Central PRETEXT III hepatoblastomas are typically indications for liver transplantation. Transplantation offers high five-year survival rates (73%). However, the associated morbidity, healthcare system costs, and limited availability make it necessary to explore alternative options. Series have reported the successful application of the ALPPS procedure in PRETEXT II and PRETEXT III hepatoblastomas in other locations. Therapeutically induced hypertrophy, characterized by an increase in the volume of healthy tissue in unaffected lobes or segments, enabled the resection of previously deemed unresectable lesions. The patients experienced uncomplicated postoperative courses and expected reduction in tumor markers. Chemotherapy selection followed the guidelines outlined in Block C of the SIOPEL IV protocol. Conclusions: ALPPS hepatectomy is a viable therapeutic option for patients with centrally located PRETEXT III or II hepatoblastomas.

6.
Aggress Behav ; 50(1): e22126, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38268388

RESUMEN

The autonomic nervous system (ANS) functioning has been proposed as a relevant method to characterize the therapeutic needs of intimate partner violence (IPV) perpetrators. Nevertheless, research has neglected the influence of the ANS on socio-affective functions in this population. The aim of the present study was to analyze the psychophysiological activity of IPV perpetrators (n = 52) compared to controls (n = 46) following an empathic induction task, performed through negative emotion-eliciting videos. We employed two general ANS markers (heart rate [HR] and respiratory rate [RR]), two sympathetic-related indexes (pre-ejection period [PEP] and skin conductance level [SCL]) and a parasympathetic biomarker (respiratory sinus arrhythmia [RSA]). Additionally, we explored the impact of psychophysiological activity on prosocial behavior using Hare's donation procedure. Compared to controls, IPV perpetrators reported lower HR and SCL following the task, as well as longer PEP, suggesting an attenuated sympathetic response to others' distress. No differences in the RSA response pattern were found, however, IPV perpetrators displayed lower overall RSA levels throughout the protocol, indicative of reduced parasympathetic activity. Besides, while no differences in prosocial performance were observed, greater sympathetic responses and overall parasympathetic activity predicted increased donations across the sample. Thus, a high sympathetic and parasympathetic activity might influence the occurrence of prosocial behavior. The present study provides further evidence supporting that IPV perpetrators cope differently with others' negative emotions. In line with this biopsychosocial perspective, insights are gained on the emotional processing of IPV perpetrators which, in turn, could contribute to improve IPV psychotherapeutic programs.


Asunto(s)
Violencia de Pareja , Arritmia Sinusal Respiratoria , Humanos , Altruismo , Sistema Nervioso Autónomo , Emociones
7.
Rev Esp Enferm Dig ; 116(1): 41-42, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37204091

RESUMEN

Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten intake. Celiac hepatitis is the most common hepatic manifestation of CD, it usually responds to a gluten-free diet (GFD) and is sometimes the only manifestation in paucisymptomatic CD. Through this descriptive observational study, we determined the prevalence of liver abnormalities upon diagnosis of CD. A total of 140 patients were included. The prevalence of alterations in liver markers at diagnosis of CD was 47%. In 2.9% of patients, liver abnormalities were the only manifestation at diagnosis. A higher prevalence of liver alterations was found in those patients who presented a more severe histological alteration (MARSH 3c).


Asunto(s)
Enfermedad Celíaca , Enfermedades Inflamatorias del Intestino , Hepatopatías , Humanos , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Hepatopatías/epidemiología , Hepatopatías/etiología , Dieta Sin Gluten , Biopsia
8.
J Neurol ; 271(4): 1599-1609, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38085343

RESUMEN

BACKGROUND AND OBJECTIVES: Serum biomarkers are emerging as useful prognostic tools for multiple sclerosis (MS); however, long-term studies are lacking. We aimed to evaluate the long-term prognostic value of the serum levels of neurofilament light chain (NfL), total tau, glial fibrillary acidic protein (GFAP), and chitinase 3-like-1 (CHI3L1) measured close to the time of MS onset. METHODS: In this retrospective, exploratory, observational, case and controls study, patients with relapsing-remitting MS (RRMS) with available baseline serum samples and prospectively follow-up in our MS unit for a long time were selected based on their clinical evolution to form two groups: (1) a benign RRMS (bRRMS) group, defined as patients with an Expanded Disability Status Scale (EDSS) score of ≤ 3 at ≥ 10 years of follow-up; (2) an aggressive RRMS (aRRMS) group, defined as patients with an EDSS score of ≥ 6 at ≤ 15 years of follow-up. An age-matched healthy control (HC) group was selected. NfL, total tau, and GFAP serum levels were quantified using a single-molecule array (SIMOA), and CHI3L1 was quantified using ELISA. RESULTS: Thirty-one patients with bRRMS, 19 with aRRMS, and 10 HC were included. The median follow-up time from sample collection was 17.74 years (interquartile range, 14.60-20.37). Bivariate and multivariate analyses revealed significantly higher NfL and GFAP levels in the aRRMS group than in the bRRMS group. A receiver operating characteristic curve analysis identified serum NfL level as the most efficient marker for distinguishing aRRMS from bRRMS. DISCUSSION: This proof-of-concept study comparing benign and aggressive RRMS groups reinforces the potential role of baseline NfL serum levels as a promising long-term disability prognostic marker. In contrast, serum GFAP, total tau, and CHI3L1 levels demonstrated a lower or no ability to differentiate between the long-term outcomes of RRMS.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Estudios Retrospectivos , Estudios de Seguimiento , Filamentos Intermedios , Biomarcadores , Proteínas de Neurofilamentos , Proteína Ácida Fibrilar de la Glía
9.
Ocul Surf ; 32: 26-38, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38151073

RESUMEN

PURPOSE: Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) is upregulated in various pathophysiological contexts, where it has a diverse repertoire of immunoregulatory functions. Herein, we investigated the expression and function of TSG-6 during corneal homeostasis and after injury. METHODS: Human corneas, eyeballs from BALB/c (TSG-6+/+), TSG-6+/- and TSG-6-/- mice, human immortalized corneal epithelial cells and murine corneal epithelial progenitor cells were prepared for immunostaining and real time PCR analysis of endogenous expression of TSG-6. Mice were subjected to unilateral corneal debridement or alkali burn (AB) injuries and wound healing assessed over time using fluorescein stain, in vivo confocal microscopy and histology. RESULTS: TSG-6 is endogenously expressed in the human and mouse cornea and established corneal epithelial cell lines and is upregulated after injury. A loss of TSG-6 has no structural and functional effect in the cornea during homeostasis. No differences were noted in the rate of corneal epithelial wound closure between BALB/c, TSG-6+/- and TSG-6-/- mice. TSG-6-/- mice presented decreased inflammatory response within the first 24 h of injury and accelerated corneal wound healing following AB when compared to control mice. CONCLUSION: TSG-6 is endogenously expressed in the cornea and upregulated after injury where it propagates the inflammatory response following chemical injury.


Asunto(s)
Quemaduras Químicas , Moléculas de Adhesión Celular , Epitelio Corneal , Quemaduras Oculares , Cicatrización de Heridas , Animales , Humanos , Ratones , Quemaduras Químicas/metabolismo , Quemaduras Químicas/patología , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Córnea/metabolismo , Córnea/patología , Lesiones de la Cornea/inducido químicamente , Lesiones de la Cornea/genética , Lesiones de la Cornea/metabolismo , Lesiones de la Cornea/patología , Modelos Animales de Enfermedad , Epitelio Corneal/metabolismo , Epitelio Corneal/patología , Quemaduras Oculares/inducido químicamente , Quemaduras Oculares/genética , Quemaduras Oculares/metabolismo , Quemaduras Oculares/patología , Queratitis/metabolismo , Queratitis/patología , Ratones Endogámicos BALB C , Ratones Noqueados , Microscopía Confocal , Reacción en Cadena en Tiempo Real de la Polimerasa , Cicatrización de Heridas/fisiología
10.
Natl Sci Rev ; 11(1): nwad138, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38116089

RESUMEN

New particle formation (NPF) in the tropical free troposphere (FT) is a globally important source of cloud condensation nuclei, affecting cloud properties and climate. Oxidized organic molecules (OOMs) produced from biogenic volatile organic compounds are believed to contribute to aerosol formation in the tropical FT, but without direct chemical observations. We performed in situ molecular-level OOMs measurements at the Bolivian station Chacaltaya at 5240 m above sea level, on the western edge of Amazonia. For the first time, we demonstrate the presence of OOMs, mainly with 4-5 carbon atoms, in both gas-phase and particle-phase (in terms of mass contribution) measurements in tropical FT air from Amazonia. These observations, combined with air mass history analyses, indicate that the observed OOMs are linked to isoprene emitted from the rainforests hundreds of kilometers away. Based on particle-phase measurements, we find that these compounds can contribute to NPF, at least the growth of newly formed nanoparticles, in the tropical FT on a continental scale. Thus, our study is a fundamental and significant step in understanding the aerosol formation process in the tropical FT.

11.
Am J Trop Med Hyg ; 109(6): 1298-1302, 2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-37972339

RESUMEN

Dengue virus (DENV) is the etiological agent of dengue fever (DF), which is among the most prevalent vector-borne diseases in the tropics. In 2022, the Colombian health surveillance system reported more than 69,000 cases of DF. As part of a hospital-based fever surveillance study, acute-phase sera were collected from 4,545 patients with suspected dengue between 2020 and 2023 in three municipalities of Colombia. Combined reverse transcription-polymerase chain reaction and antigen rapid testing confirmed that 376 patients (8.3%) had DF. The virus was isolated in cell culture from 166 of these patients (44.1%), and genome sequencing was performed successfully on 122 (73.5%). Three DENV serotypes (1, 2, and 3) were identified. Phylogenetic analyses of the DENV-2 sequences revealed that 42 of 50 of the isolates (84%) belonged to the DENV-2 cosmopolitan genotype lineage, clustering with sequences from Asia, Peru, and Brazil. We report the detection, isolation, and whole-genome sequencing (11 Kb) of the DENV-2 cosmopolitan genotype and its recent introduction to Colombia.


Asunto(s)
Virus del Dengue , Dengue , Humanos , Serogrupo , Filogenia , Colombia/epidemiología , Genotipo
12.
Matrix Biol ; 124: 23-38, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37949327

RESUMEN

The prevalence of dry eye disease (DED) ranges from ∼5 to 50 % and its associated symptoms decrease productivity and reduce the quality of life. Approximately 85 % of all DED cases are caused by Meibomian gland dysfunction (MGD). As humans and mice age, their Meibomian glands (MGs) undergo age-related changes resulting in age related-MGD (ARMGD). The precise cause of ARMGD remains elusive, which makes developing therapies extremely challenging. We previously demonstrated that a hyaluronan (HA)-rich matrix exists surrounding the MG, regulating MG morphogenesis and homeostasis. Herein, we investigated whether changes to the HA matrix in the MG throughout life contributes towards ARMGD, and whether altering this HA matrix can prevent ARMGD. For such, HA synthase (Has) knockout mice were aged and compared to age matched wild type (wt) mice. MG morphology, lipid production, PPARγ expression, basal cell proliferation, stem cells, presence of atrophic glands and MG dropout were analyzed at 8 weeks, 6 months, 1 year and 2 years of age and correlated with the composition of the HA matrix. We found that as mice age, there is a loss of HA expression in and surrounding the MGs of wt mice, while, in contrast, Has1-/-Has3-/- mice present a significant increase in HA expression through Has2 upregulation. At 1 year, Has1-/-Has3-/- mice present significantly enlarged MGs, compared to age-matched wt mice and compared to all adult mice. Thus, Has1-/-Has3-/- mice continue to develop new glandular tissue as they age, instead of suffering MG atrophy. At 2 years, Has1-/-Has3-/- mice continue to present significantly larger MGs compared to age-matched wt mice. Has1-/-Has3-/- mice present increased lipid production, increased PPARγ expression and an increase in the number of proliferating cells when compared to wt mice at all-time points analyzed. Taken together, our data shows that a loss of the HA matrix surrounding the MG as mice age contributes towards ARMGD, and increasing Has2 expression, and consequently HA levels, prevents ARMGD in mice.


Asunto(s)
Ácido Hialurónico , Disfunción de la Glándula de Meibomio , Ratones , Humanos , Animales , Anciano , Ácido Hialurónico/metabolismo , Glucuronosiltransferasa , PPAR gamma/genética , Calidad de Vida , Hialuronano Sintasas/genética , Ratones Noqueados , Lípidos
13.
Ocul Surf ; 30: 298-306, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37979775

RESUMEN

Meibomian glands (MGs), located within the tarsal plate of the eyelid, secrete meibum which is the lipid-rich secretion necessary for stabilizing the tear film and preventing tear evaporation. Changes in the quality and quantity of meibum produced causes MG dysfunction (MGD), the leading cause of evaporative dry eye disease (EDED). MGD is an underdiagnosed disease and it is estimated that, in the US, approximately 70 % of the population over 60 have MGD. Three forms of MGD occur based on their meibum secretion: hyposecretory, obstructive, and hypersecretory MGD. The pathophysiology of MGD remains poorly understood, however aging is the primary risk factor. With age, MGs undergo various age-related changes, including decreased acinar basal cell proliferation, hyperkeratinization, MG atrophy, and eventual MG drop-out, leading to age-related MGD (ARMGD). Additionally, studies have suggested that MGs can suffer inflammatory cell infiltration and changes innervation patterns with aging, which could also contribute towards ARMGD. This review focuses on how the aging process affects the MG, and more importantly, how age-related changes to the MG can lead to MG atrophy and MG drop-out, ultimately leading to ARMGD. This review also highlights the most recent developments in potential therapeutic interventions for ARMGD.


Asunto(s)
Síndromes de Ojo Seco , Enfermedades de los Párpados , Disfunción de la Glándula de Meibomio , Humanos , Glándulas Tarsales/patología , Lágrimas , Envejecimiento , Atrofia/patología , Enfermedades de los Párpados/patología
14.
Invest Ophthalmol Vis Sci ; 64(13): 48, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37906057

RESUMEN

Purpose: Limbal epithelial stem cells (LESCs) reside within a LSC niche (LSCN). We recently identified that hyaluronan (HA) is a major constituent of the LSCN, and that HA is necessary for maintaining LESCs in the "stem cell" state, both in vitro and in vivo. Herein, we characterized the LSCN to identify key components of the HA-specific LSCN. Methods: The cornea and limbal rim were dissected from mouse corneas, subjected to mRNA extraction, and sequenced using a NextSeq 500 (Illumina) and data processed using CLC Genomics Workbench 20 (Qiagen) and the STRING database to identify key components of the LSCN. Their expression was confirmed by real-time PCR, Western blotting, and immunohistochemistry. Furthermore, the differential expression of key compounds in different corneal cell types were determined with single-cell RNA sequencing. Results: We identified that the hyaladherins inter-alpha-inhibitor (IαI), TSG-6 and versican are highly expressed in the limbus. Specifically, HA/HC complexes are present in the LSCN, in the stroma underlying the limbal epithelium, and surrounding the limbal vasculature. For IαI, heavy chains 5 and 2 (HC5 and HC2) were found to be the most highly expressed HCs in the mouse and human limbus and were associate with HA-forming HA/HC-specific matrices. Conclusions: The LSCN contains HA/HC complexes, which have been previously correlated with stem cell niches. The identification of HA/HC complexes in the LSCN could serve as a new therapeutic avenue for treating corneal pathology. Additionally, HA/HC complexes could be used as a substrate for culturing LESCs before LESC transplantation.


Asunto(s)
Córnea , Nicho de Células Madre , Humanos , Animales , Ratones , Western Blotting , Bases de Datos Factuales , Epitelio , Ácido Hialurónico
15.
Ocul Surf ; 30: 168-178, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37742739

RESUMEN

PURPOSE: Lumican is a major extracellular matrix (ECM) component in the cornea that is upregulated after injury and promotes corneal wound healing. We have recently shown that peptides designed based on the 13 C-terminal amino acids of lumican (LumC13 and LumC13C-A) are able to recapitulate the effects of lumican on promoting corneal wound healing. Herein we used computational chemistry to develop peptide mimetics derived from LumC13C-A with increased stability and half-life that are biologically active and non-toxic, thereby promoting corneal wound healing with increased pharmacological potential. METHODS: Different peptides staples were rationalized using LumC13C-A sequence by computational chemistry, docked to TGFßRI and the interface binding energies compared. Lowest scoring peptides were synthesized, and the toxicity of peptides tested using CCK8-based cell viability assay. The efficacy of the stapled peptides at promoting corneal wound healing was tested using a proliferation assay, an in vitro scratch assay using human corneal epithelial cells and an in vivo murine corneal debridement wound healing model. RESULTS: Binding free energies were calculated using MMGBSA algorithm, and peptides LumC13C and LumC13S5 displayed superior binding to ALK5 compared to the non-stapled peptide LumC13C-A. The presence of the hydrocarbon staple in LumC13C enhances the stability of the α-helical conformation, thereby facilitating more optimal interactions with the ALK5 receptor. The stapled peptides do not present cytotoxic effects on human corneal epithelial cells at a 300 nM concentration. Similar to lumican and LumC13C-A, both C13C and LumC13S5 significantly promote corneal wound healing both in vitro and in vivo. CONCLUSIONS: Highly stable and non-toxic stapled peptides designed based on LumC13, significantly promote corneal wound healing. As a proof of principle, our data shows that more stable and pharmacologically relevant peptides can be designed based on endogenous peptide sequences for treating various corneal pathologies.


Asunto(s)
Lesiones de la Cornea , Epitelio Corneal , Humanos , Animales , Ratones , Lumican/metabolismo , Lumican/farmacología , Córnea/patología , Lesiones de la Cornea/metabolismo , Cicatrización de Heridas , Péptidos/farmacología , Péptidos/metabolismo , Epitelio Corneal/metabolismo
16.
Biomolecules ; 13(9)2023 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-37759785

RESUMEN

A buildup of reactive oxygen species (ROS) occurs in virtually all pathological conditions. Hyaluronan (HA) is a major extracellular matrix component and is susceptible to oxidation by reactive oxygen species (ROS), yet the precise chemical structures of oxidized HA products (oxHA) and their physiological properties remain largely unknown. This study characterized the molecular weight (MW), structures, and physiological properties of oxHA. For this, high-molecular-weight HA (HMWHA) was oxidized using increasing molar ratios of hydrogen peroxide (H2O2) or hypochlorous acid (HOCl). ROS lead to the fragmentation of HA, with the oxHA products produced by HOCl exhibiting an altered chemical structure while those produced by H2O2 do not. HMWHA promotes the viability of human corneal epithelial cells (hTCEpi), while low MWHA (LMWHA), ultra-LMWHA (ULMWHA), and most forms of oxHA do not. HMWHA and LMWHA promote hTCEpi proliferation, while ULMWHA and all forms of oxHA do not. LMWHA and some forms of oxHA promote hTCEpi migration, while HMWHA does not. Finally, all native forms of HA and oxHA produced by HOCl promote in vivo corneal wound healing, while oxHA produced by H2O2 does not. Taken together, our results show that HA fragmentation by ROS can alter the physiological activity of HA by altering its MW and structure.


Asunto(s)
Ácido Hialurónico , Peróxido de Hidrógeno , Humanos , Ácido Hialurónico/farmacología , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno , Córnea , Cicatrización de Heridas
17.
Free Radic Biol Med ; 207: 308-319, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37597786

RESUMEN

Pregnancy requires a high demand of energy, which leads to an increase of oxidative stress. The aim of this study was to assess the oxidative status in 200 couples of pregnant women-newborns at the time of delivery, for the first time, who gave birth in two University Hospitals from the province of Seville. Recruited women filled an epidemiological questionnaire with their demographic characteristics and dietary habits during pregnancy. At the time of delivery, both maternal and cord blood samples were collected. Protein oxidation, superoxide dismutase, and catalase levels were measured to assess the oxidative status of these women, together with the levels of vitamins D, B12, Zn, Se, and Cu. Our results showed a tendency for all biomarkers measured to be higher in cord blood than in maternal blood. For the correlations established between the OS markers and sociodemographic characteristics, only significant differences for carbonyl groups values were found on both maternal and cord blood, relating these higher values to the use of insecticides in the women's homes. For newborns, only a significant correlation was detected between antioxidant enzymes and the newborn's weight, specifically for superoxide dismutase activity. Additionally, the higher values obtained in cord blood might suggest metabolization, while a higher production of ROS and antioxidant enzymes might be required to maintain the balance. Measured levels for Se were similar in both maternal and cord blood, unlike Cu and Zn, where higher levels were found for maternal blood than cord blood, indicating a correlation between maternal Se values and SOD as OS biomarker. Furthermore, vitamin D levels were around the optimum values established, finding a relationship between vitamin D and new-born's height, unlike for vitamin B12 values, where a correlation with maternal food consumption characteristics was established. Overall values were inside normal ranges and consistent for our population.


Asunto(s)
Antioxidantes , Superóxido Dismutasa , Recién Nacido , Embarazo , Humanos , Femenino , España , Estudios Prospectivos , Vitamina D , Relaciones Madre-Hijo
18.
Biomolecules ; 13(7)2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37509064

RESUMEN

The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range.


Asunto(s)
Lesiones de la Cornea , Queratitis , Infecciones por Pseudomonas , Animales , Ratones , Pseudomonas aeruginosa , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Lesiones de la Cornea/tratamiento farmacológico , Péptidos/uso terapéutico , Cicatrización de Heridas
19.
Differentiation ; 132: 41-50, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37202278

RESUMEN

The Meibomian gland (MG) is an indispensable adnexal structure of eye that produces meibum, an important defensive component for maintaining ocular homeostasis. Normal development and maintenance of the MGs is required for ocular health since atrophic MGs and disturbances in composition and/or secretion of meibum result in major ocular pathologies, collectively termed as Meibomian gland dysfunction (MGD). Currently available therapies for MGD merely provide symptomatic relief and do not treat the underlying deficiency of the MGs. Hence, a thorough understanding of the timeline of MG development, maturation and aging is required for regenerative purposes along with signaling molecules & pathways controlling proper differentiation of MG lineage in mammalian eye. Understanding the factors that contribute to the development of MGs, developmental abnormalities of MGs, and changes in the quality & quantity of meibum with developing phases of MGs are essential for developing potential treatments for MGD. In this review, we compiled a timeline of events and the factors involved in the structural and functional development of MGs and the associated developmental defects of MGs during development, maturation and aging.


Asunto(s)
Enfermedades de los Párpados , Glándulas Tarsales , Animales , Glándulas Tarsales/metabolismo , Enfermedades de los Párpados/metabolismo , Lágrimas/química , Lágrimas/metabolismo , Mamíferos
20.
Healthcare (Basel) ; 11(8)2023 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37107991

RESUMEN

Adolescent dating violence has become a public health problem because of the associated high morbidity and mortality rates. Despite social awareness about dating violence, the high justification of violence among adolescents is one of the main risk factors for both perpetration and victimisation. Therefore, the objective of the present work was to evaluate the effectiveness of an educational intervention in reducing the justification of violence in adolescent dating. A quasi-experimental, longitudinal, prospective study with a control group was conducted. The study was carried out in six different schools in the Region of Murcia (Spain), and the participants were 854 students aged 14-18 years. The educational intervention was focused on reducing the justification of adolescent dating violence and consisted of 9 weekly 1 h group sessions. The Justification of Verbal/Coercive Tactics Scale (JVCT) and the Attitudes About Aggression in Dating Situations (AADS) survey were administered at baseline and at the end of the intervention in order to determine the justification of psychological and physical violence, respectively. At baseline, the justification of physical violence was at a medium-to-high level in boys (76.8%) and girls (56.7%), whereas psychological violence was much less justified. Concretely, female psychological violence was justified by 19.5% boys and 16.7% girls, while male violence was justified by 19.0% boys and 17.8% girls. After the educational intervention, a significant decrease in physical violence justification, especially in the AADS dimension of female aggression, was observed. The effect of the intervention was especially evident in psychological violence justification: a statistically significant difference was observed in the JVCT scores of boys (-6.4 and 1.3 points in the intervention and control groups, respectively; p = 0.031), but not of girls (p = 0.594). In conclusion, the educational intervention was adequate to reduce the justification of dating violence among the participants. It may provide adolescents with the skills and resources necessary to confront and resolve conflicts in relationships in a non-violent manner.

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