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1.
Biol Open ; 13(2)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38319134

RESUMEN

Limb regeneration in salamanders is achieved by a complex coordination of various biological processes and requires the proper integration of new tissue with old. Among the tissues found inside the limb, the skeleton is the most prominent component, which serves as a scaffold and provides support for locomotion in the animal. Throughout the years, researchers have studied the regeneration of the appendicular skeleton in salamanders both after limb amputation and as a result of fracture healing. The final outcome has been widely seen as a faithful re-establishment of the skeletal elements, characterised by a seamless integration into the mature tissue. The process of skeletal integration, however, is not well understood, and several works have recently provided evidence of commonly occurring flawed regenerates. In this Review, we take the reader on a journey through the course of bone formation and regeneration in salamanders, laying down a foundation for critically examining the mechanisms behind skeletal integration. Integration is a phenomenon that could be influenced at various steps of regeneration, and hence, we assess the current knowledge in the field and discuss how early events, such as tissue histolysis and patterning, influence the faithful regeneration of the appendicular skeleton.


Asunto(s)
Locomoción , Osteogénesis , Animales , Humanos , Investigadores , Urodelos
2.
J Mammary Gland Biol Neoplasia ; 29(1): 5, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416267

RESUMEN

The three-dimensional (3D) structure of the ductal epithelium and the surrounding extracellular matrix (ECM) are integral aspects of the breast tissue, and they have important roles during mammary gland development, function and malignancy. However, the architecture of the branched mammary epithelial network is poorly recapitulated in the current in vitro models. 3D bioprinting is an emerging approach to improve tissue-mimicry in cell culture. Here, we developed and optimized a protocol for 3D bioprinting of normal and cancerous mammary epithelial cells into a branched Y-shape to study the role of cell positioning in the regulation of cell proliferation and invasion. Non-cancerous cells formed continuous 3D cell networks with several organotypic features, whereas the ductal carcinoma in situ (DCIS) -like cancer cells exhibited aberrant basal polarization and defective formation of the basement membrane (BM). Quantitative analysis over time demonstrated that both normal and cancerous cells proliferate more at the branch tips compared to the trunk region of the 3D-bioprinted cultures, and particularly at the tip further away from the branch point. The location-specific rate of proliferation was independent of TGFß signaling but invasion of the DCIS-like breast cancer cells was reduced upon the inhibition of TGFß. Thus, our data demonstrate that the 3D-bioprinted cells can sense their position in the branched network of cells and proliferate at the tips, thus recapitulating this feature of mammary epithelial branching morphogenesis. In all, our results demonstrate the capacity of the developed 3D bioprinting method for quantitative analysis of the relationships between tissue structure and cell behavior in breast morphogenesis and cancer.


Asunto(s)
Bioimpresión , Carcinoma Intraductal no Infiltrante , Humanos , Células Epiteliales , Epitelio , Factor de Crecimiento Transformador beta
3.
J Multidiscip Healthc ; 16: 3887-3895, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38084121

RESUMEN

Purpose: To analyze the adverse events reported in the pharmacovigilance of the health service provider institutions of the municipality of Monteria in the period 2018-2021. Patients and Methods: Descriptive, cross-sectional, retrospective, and quantitative approach study, the information was analyzed by statistical analysis by multiple correspondence using Orange Data Mining software; the analysis consisted of visual programming to perform interactive data exploration, to identify and differentiate associations or oppositions between different categories in space. Results: The most frequently reported adverse events were allergic reactions, with 28.5%. Female sex and adult age are the groups most prone to present these events; antibiotics were the pharmacological group that produced the most adverse events with 18.3%; the main errors that produce these events are related to prescription. Conclusion: Age and sex increase the risk of adverse drug events; most of these events are the product of erroneous prescriptions. The findings presented in this article are useful for pharmacovigilance programs in health institutions.

4.
Chem Commun (Camb) ; 59(97): 14455-14458, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37982517

RESUMEN

Time-resolved radioluminescence (TRRL) properties of the Cu(I) cluster Cu4I62- upon pulsed X-ray, ß-ray or α-particle excitation are described. The longer (>2 µs) TRRL component displays exponential decay comparable to pulsed UV excitation; however, temporal behaviour at shorter times indicates that high local excited state density provides an alternative decay channel.

5.
Cardiovasc Res ; 119(16): 2607-2622, 2023 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-37713664

RESUMEN

AIMS: Endurance exercise is associated with an increased risk of atrial fibrillation (AF). We previously established that adverse atrial remodelling and AF susceptibility induced by intense exercise in mice require the mechanosensitive and pro-inflammatory cytokine tumour necrosis factor (TNF). The cellular and mechanistic basis for these TNF-mediated effects is unknown. METHODS AND RESULTS: We studied the impact of Tnf excision, in either atrial cardiomyocytes or endothelial cells (using Cre-recombinase expression controlled by Nppa or Tie2 promoters, respectively), on the cardiac responses to six weeks of intense swim exercise training. TNF ablation, in either cell type, had no impact on the changes in heart rate, autonomic tone, or left ventricular structure and function induced by exercise training. Tnf excision in atrial cardiomyocytes did, however, prevent atrial hypertrophy, fibrosis, and macrophage infiltration as well as conduction slowing and increased AF susceptibility arising from exercise training. In contrast, endothelial-specific excision only reduced the training-induced atrial hypertrophy. Consistent with these cell-specific effects of Tnf excision, inducing TNF loss from atrial cardiomyocytes prevented activation of p38MAPKinase, a strain-dependent downstream mediator of TNF signalling, without affecting the atrial stretch as assessed by atrial pressures induced by exercise. Despite TNF's established role in innate immune responses and inflammation, neither acute nor chronic exercise training caused measurable NLRP3 inflammasome activation. CONCLUSIONS: Our findings demonstrate that adverse atrial remodelling and AF vulnerability induced by intense exercise require TNF in atrial cardiomyocytes whereas the impact of endothelial-derived TNF is limited to hypertrophy modulation. The implications of the cell autonomous effects of TNF and crosstalk between cells in the atria are discussed.


Asunto(s)
Fibrilación Atrial , Remodelación Atrial , Cardiomiopatías , Animales , Ratones , Fibrilación Atrial/etiología , Fibrilación Atrial/prevención & control , Fibrilación Atrial/patología , Miocitos Cardíacos/metabolismo , Células Endoteliales/metabolismo , Atrios Cardíacos , Factor de Necrosis Tumoral alfa/metabolismo , Cardiomiopatías/metabolismo , Hipertrofia/complicaciones , Hipertrofia/metabolismo
6.
Commun Med (Lond) ; 3(1): 97, 2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37443390

RESUMEN

BACKGROUND: The emergence of highly transmissible SARS-CoV-2 variants has led to surges in cases and the need for global genomic surveillance. While some variants rapidly spread worldwide, other variants only persist nationally. There is a need for more fine-scale analysis to understand transmission dynamics at a country scale. For instance, the Mu variant of interest, also known as lineage B.1.621, was first detected in Colombia and was responsible for a large local wave but only a few sporadic cases elsewhere. METHODS: To better understand the epidemiology of SARS-Cov-2 variants in Colombia, we used 14,049 complete SARS-CoV-2 genomes from the 32 states of Colombia. We performed Bayesian phylodynamic analyses to estimate the time of variants' introduction, their respective effective reproductive number, and effective population size, and the impact of disease control measures. RESULTS: Here, we detect a total of 188 SARS-CoV-2 Pango lineages circulating in Colombia since the pandemic's start. We show that the effective reproduction number oscillated drastically throughout the first two years of the pandemic, with Mu showing the highest transmissibility (Re and growth rate estimation). CONCLUSIONS: Our results reinforce that genomic surveillance programs are essential for countries to make evidence-driven interventions toward the emergence and circulation of novel SARS-CoV-2 variants.


Colombia reported its first COVID-19 case on 6th March 2020. By April 2022, the country had reported over 6 million infections and over 135,000 deaths. Here, we aim to understand how SARS-CoV-2, the virus that causes COVID-19, spread through Colombia over this time and how the predominant version of the virus (variant) changed over time. We found that there were multiple introductions of different variants from other countries into Colombia during the first two years of the pandemic. The Gamma variant was dominant earlier in 2021 but was replaced by the Delta variant. The Mu variant had the highest potential to be transmitted. Our findings provide valuable insights into the pandemic in Colombia and highlight the importance of continued surveillance of the virus to guide the public health response.

7.
J Med Case Rep ; 17(1): 218, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37194080

RESUMEN

BACKGROUND: Streptococcus cristatus is a member of the Mitis streptococcus group. Like other members of this group, it resides on mucosal surfaces of the oral cavity. However, little is known about its ability to cause disease as there are only a handful of cases in the literature. Two of these cases involved infective endocarditis with significant complications. However, these cases involved additional microbes, limiting the inferences about the pathogenicity of Streptococcus cristatus. CASE PRESENTATION: A 59-year-old African American male with end-stage cryptogenic cirrhosis and ascites presented with fatigue and confusion. A paracentesis was negative for spontaneous bacterial peritonitis, but two separate blood cultures grew Streptococcus cristatus. Our patient had a history of dental caries and poor oral hygiene, which were likely the source of the infection. Echocardiograms revealed new aortic regurgitation, indicating "possible endocarditis" per the Modified Duke Criteria. However, since his clinical picture and cardiac function were reassuring, we elected against treatment for infective endocarditis. He was treated for bacteremia with a 2-week course of cephalosporins consisting of 8 days of ceftriaxone, transitioning to cefpodoxime after discharge. Despite having end-stage liver disease, our patient did not experience any significant complications from the infection. CONCLUSION: A patient with end-stage cirrhosis and poor oral hygiene developed bacteremia with an oral bacterium called Streptococcus cristatus. Unlike previous cases in literature, our patient did not meet criteria for a definitive diagnosis of infective endocarditis, and he experienced no other complications from the infection. This suggests coinfectants may have been primarily responsible for the severe cardiac sequelae in prior cases, whereas isolated Streptococcus cristatus infection may be relatively mild.


Asunto(s)
Bacteriemia , Caries Dental , Endocarditis Bacteriana , Endocarditis , Infecciones Estreptocócicas , Humanos , Masculino , Persona de Mediana Edad , Higiene Bucal/efectos adversos , Caries Dental/complicaciones , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/diagnóstico , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/diagnóstico , Endocarditis/complicaciones , Streptococcus pyogenes , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología
8.
Eur J Cell Biol ; 102(2): 151314, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37058825

RESUMEN

The small GTPase Ras is frequently mutated in cancer and a driver of tumorigenesis. The recent years have shown great progress in drug-targeting Ras and understanding how it operates on the plasma membrane. We now know that Ras is non-randomly organized into proteo-lipid complexes on the membrane, called nanoclusters. Nanoclusters contain only a few Ras proteins and are necessary for the recruitment of downstream effectors, such as Raf. If tagged with fluorescent proteins, the dense packing of Ras in nanoclusters can be analyzed by Förster/ fluorescence resonance energy transfer (FRET). Loss of FRET can therefore report on decreased nanoclustering and any process upstream of it, such as Ras lipid modifications and correct trafficking. Thus, cellular FRET screens employing Ras-derived fluorescence biosensors are potentially powerful tools to discover chemical or genetic modulators of functional Ras membrane organization. Here we implement fluorescence anisotropy-based homo-FRET measurements of Ras-derived constructs labelled with only one fluorescent protein on a confocal microscope and a fluorescence plate reader. We show that homo-FRET of both H-Ras- and K-Ras-derived constructs can sensitively report on Ras-lipidation and -trafficking inhibitors, as well as on genetic perturbations of proteins regulating membrane anchorage. By exploiting the switch I/II-binding Ras-dimerizing compound BI-2852, this assay is also suitable to report on the engagement of the K-Ras switch II pocket by small molecules such as AMG 510. Given that homo-FRET only requires one fluorescent protein tagged Ras construct, this approach has significant advantages to create Ras-nanoclustering FRET-biosensor reporter cell lines, as compared to the more common hetero-FRET approaches.


Asunto(s)
Transferencia Resonante de Energía de Fluorescencia , Proteínas , Línea Celular , Polarización de Fluorescencia , Lípidos
9.
Inorg Chem ; 62(12): 4847-4852, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-36913615

RESUMEN

Reaction of MBr2 with 3 equiv of [K(18-crown-6)][O2N2CPh3] generates the trityl diazeniumdiolate complexes [K(18-crown-6)][M(O2N2CPh3)3] (M = Co, 2; Fe, 3) in good yields. Irradiation of 2 and 3 using 371 nm light led to NO formation in 10 and 1% yields (calculated assuming a maximum of 6 equiv of NO produced per complex), respectively. N2O was also formed during the photolysis of 2, in 63% yield, whereas photolysis of 3 led to the formation of N2O, as well as Ph3CN(H)OCPh3, in 37 and 5% yields, respectively. These products are indicative of diazeniumdiolate fragmentation via both C-N and N-N bond cleavage pathways. In contrast, oxidation of complexes 2 and 3 with 1.2 equiv of [Ag(MeCN)4][PF6] led to N2O formation but no NO formation, suggesting that diazeniumdiolate fragmentation occurs exclusively via C-N bond cleavage under these conditions. While the photolytic yields of NO are modest, they represent a 10- to 100-fold increase compared to the previously reported Zn congener, suggesting that the presence of a redox-active metal center favors NO formation upon trityl diazeniumdiolate fragmentation.

10.
Mol Psychiatry ; 28(7): 2975-2984, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36725899

RESUMEN

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.


Asunto(s)
Miedo , Trastornos por Estrés Postraumático , Humanos , Estudios Longitudinales , Miedo/fisiología , Amígdala del Cerebelo , Giro del Cíngulo/patología , Imagen por Resonancia Magnética , Corteza Prefrontal/patología
11.
Parasit Vectors ; 16(1): 5, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36604762

RESUMEN

BACKGROUND: The genus Borrelia is composed of two well-defined monophyletic groups, the Borrelia burgdorferi sensu lato complex (Bb) and the relapsing fever (RF) group borreliae. Recently, a third group, associated with reptiles and echidnas, has been described. In general, RF group borreliae use rodents as reservoir hosts; although neotropical bats may also be involved as important hosts, with scarce knowledge regarding this association. The objective of this study was to detect the presence of Borrelia spp. DNA in bats from the department of Córdoba in northwest Colombia. METHODS: During September 2020 and June 2021, 205 bats were captured in six municipalities of Córdoba department, Colombia. Specimens were identified using taxonomic keys and DNA was extracted from spleen samples. A Borrelia-specific real-time PCR was performed for the 16S rRNA gene. Fragments of the 16S rRNA and flaB genes were amplified in the positive samples by conventional PCR. The detected amplicons were sequenced by the Sanger method. Phylogenetic reconstruction was performed in IQ-TREE with maximum likelihood based on the substitution model TPM3+F+I+G4 with bootstrap values deduced from 1000 replicates. RESULTS: Overall, 10.2% (21/205) of the samples were found positive by qPCR; of these, 81% (17/21) and 66.6% (14/21) amplified 16S rRNA and flaB genes, respectively. qPCR-positive samples were then subjected to conventional nested and semi-nested PCR to amplify 16S rRNA and flaB gene fragments. Nine positive samples for both genes were sequenced, and seven and six sequences were of good quality for the 16S rRNA and flaB genes, respectively. The DNA of Borrelia spp. was detected in the insectivorous and fruit bats Artibeus lituratus, Carollia perspicillata, Glossophaga soricina, Phyllostomus discolor, and Uroderma sp. The 16S rRNA gene sequences showed 97.66-98.47% identity with "Borrelia sp. clone Omi3," "Borrelia sp. RT1S," and Borrelia sp. 2374; the closest identities for the flaB gene were 94.02-98.04% with "Borrelia sp. Macaregua." For the 16S rRNA gene, the phylogenetic analysis showed a grouping with "Candidatus Borrelia ivorensis" and "Ca. Borrelia africana," and for the flaB gene showed a grouping with Borrelia sp. Macaregua and Borrelia sp. Potiretama. The pathogenic role of the Borrelia detected in this study is unknown. CONCLUSIONS: We describe the first molecular evidence of Borrelia spp. in the department of Córdoba, Colombia, highlighting that several bat species harbor Borrelia spirochetes.


Asunto(s)
Borrelia , Quirópteros , Animales , Borrelia/genética , ARN Ribosómico 16S/genética , Filogenia , Colombia/epidemiología , Funciones de Verosimilitud , ADN Bacteriano/genética
12.
Methods Mol Biol ; 2562: 155-163, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36272073

RESUMEN

The axolotl is a great model for studying cartilage, bone and joint regeneration, fracture healing, and evolution. Stainings such as Alcian Blue/Alizarin Red have become workhorses in skeletal analyses, but additional methods complement the detection of different skeletal matrices. Here we describe protocols for studying skeletal biology in axolotls, particularly Alcian Blue/Alizarin Red staining, microcomputed tomography (µCT) scan and live staining of calcified tissue. In addition, we describe a method for decalcification of skeletal elements to ease sectioning.


Asunto(s)
Ambystoma mexicanum , Biología , Animales , Azul Alcián , Microtomografía por Rayos X , Coloración y Etiquetado
13.
Elife ; 112022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-36218256

RESUMEN

Early events during axolotl limb regeneration include an immune response and the formation of a wound epithelium. These events are linked to a clearance of damaged tissue prior to blastema formation and regeneration of the missing structures. Here, we report the resorption of calcified skeletal tissue as an active, cell-driven, and highly regulated event. This process, carried out by osteoclasts, is essential for a successful integration of the newly formed skeleton. Indeed, the extent of resorption is directly correlated with the integration efficiency, and treatment with zoledronic acid resulted in osteoclast function inhibition and failed tissue integration. Moreover, we identified the wound epithelium as a regulator of skeletal resorption, likely releasing signals involved in recruitment/differentiation of osteoclasts. Finally, we reported a correlation between resorption and blastema formation, particularly, a coordination of resorption with cartilage condensation. In sum, our results identify resorption as a major event upon amputation, playing a critical role in the overall process of skeletal regeneration.


Asunto(s)
Ambystoma mexicanum , Osteoclastos , Animales , Ambystoma mexicanum/fisiología , Ácido Zoledrónico , Extremidades/fisiología , Esqueleto
14.
Dev Cell ; 57(20): 2350-2364.e7, 2022 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-36283390

RESUMEN

Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer. During invasion, the encapsulating DCIS basement membrane (BM) is compromised, and tumor cells invade the surrounding stroma. The mechanisms that regulate functional epithelial BMs in vivo are poorly understood. Myosin-X (MYO10) is a filopodia-inducing protein associated with metastasis and poor clinical outcome in invasive breast cancer (IBC). We identify elevated MYO10 expression in human DCIS and IBC, and this suggests links with disease progression. MYO10 promotes filopodia formation and cell invasion in vitro and cancer-cell dissemination from progressively invasive human DCIS xenografts. However, MYO10-depleted xenografts are more invasive. These lesions exhibit compromised BMs, poorly defined borders, and increased cancer-cell dispersal and EMT-marker-positive cells. In addition, cancer spheroids are dependent on MYO10-filopodia to generate a near-continuous extracellular matrix boundary. Thus, MYO10 is protective in early-stage breast cancer, correlating with tumor-limiting BMs, and pro-invasive at later stages, facilitating cancer-cell dissemination.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Seudópodos/metabolismo , Neoplasias de la Mama/patología , Miosinas/metabolismo , Membrana Basal/metabolismo , Carcinoma Ductal de Mama/metabolismo
15.
Inorg Chem ; 61(38): 14924-14928, 2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36098655

RESUMEN

Exposure of [K(18-crown-6)(THF)2][CPh3] (THF = tetrahydrofuran; Ph = phenyl) to an atmosphere of nitric oxide (NO) cleanly generates [K(18-crown-6)][O2N2CPh3] (1) in excellent yields. A subsequent reaction of [ZnCl2(THF)2] with 3 equiv of 1 affords the C-diazeniumdiolate complex [K(18-crown-6)][Zn(O2N2CPh3)3] (2). Both 1 and 2 were characterized by 1H and 13C{1H} NMR spectroscopy, and their structures were confirmed by X-ray crystallography. Photolysis of 2 using 371 nm light resulted in the formation of three trityl-containing products, namely, Ph3CH, 9-phenylfluorene, and Ph3CN(H)OCPh3 (3). In addition, we detected nitrous oxide (N2O), as well as small amounts of NO in the reaction mixture. In contrast, oxidation of 2 with 1.2 equiv of [Ag(MeCN)4][PF6] resulted in the formation of O(CPh3)2 as the major trityl-containing product; N2O was also detected in the reaction mixture, but NO was not apparently formed in this case. The observation of these fragmentation products indicates that the [O2N2CPh3]- ligand is susceptible to both C-N bond and N-N bond cleavage. Moreover, the different product distributions suggest that [O2N2CPh3]- is susceptible to different modes of fragmentation.


Asunto(s)
Óxido Nítrico , Óxido Nitroso , Compuestos Azo , Éteres Corona , Furanos , Ligandos , Estrés Oxidativo , Fotólisis
16.
Travel Med Infect Dis ; 49: 102427, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35963556

RESUMEN

INTRODUCTION: Although more than half of the world's population is already vaccinated, the appearance of new variants of concern puts public health at risk due to the generation of new immunogens against the virus as a crucial and relevant strategy in the control of these new variants. METHODS: A preclinical study used a potential vaccine candidate (RBD, SARS-CoV-2). Four groups of BALB/c mice were used, a control group, an adjuvant group, a group inoculated with one dose of RBD subunit protein, and the fourth group inoculated with two doses of RBD subunit protein. RESULTS: No inflammatory or cellular changes were shown in the mice's anatomopathological evaluation. Higher kinetics and 75% seroconversion were obtained in the mice inoculated with two doses of RBD (P < 0.0001). CONCLUSIONS: The application of two doses of the RBD vaccine candidate in BALB/c mice proved safe and immunogenic against SARS-CoV-2.


Asunto(s)
COVID-19 , Vacunas Virales , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos BALB C , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus
17.
BMC Infect Dis ; 22(1): 644, 2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35883062

RESUMEN

BACKGROUND: The ability of SARS-CoV-2 to remain in asymptomatic individuals facilitates its dissemination and makes its control difficult. OBJECTIVE: To establish a cohort of asymptomatic individuals, change to the symptomatic status, and determine the most frequent clinical manifestations.  METHODS: Between April 9 and August 9, 2020, molecular diagnosis of SARS-CoV-2 infection was confirmed in 154 asymptomatic people in contact with subjects diagnosed with COVID-19. Nasopharyngeal swabs were performed on these people in different hospitals in Córdoba, the Caribbean area of Colombia. The genes E, RdRp, and N were amplified with RT-qPCR. Based on the molecular results and the Cq values, the patients were subsequently followed up through telephone calls to verify their health conditions. RESULTS: Overall, of 154 asymptomatic individuals, 103 (66.9%) remained asymptomatic, and 51 (33.1%) changed to symptomatic. The most frequent clinical manifestations in young people were anosmia and arthralgia. Adults showed cough, ageusia, and odynophagia; in the elderly were epigastralgia, dyspnea, and headache. Mortality was 8%. CONCLUSIONS: A proportion of 33% of presymptomatic individuals was found, of which four of them died. This high rate could indicate a silent transmission, contributing significantly to the epidemic associated with SARS-CoV-2.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adolescente , Adulto , Anciano , COVID-19/diagnóstico , COVID-19/epidemiología , Colombia/epidemiología , Tos , Humanos , Salud Pública , SARS-CoV-2/genética
18.
Open Biol ; 12(6): 220078, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35728623

RESUMEN

In processes such as development and regeneration, where large cellular and tissue rearrangements occur, cell fate and behaviour are strongly influenced by tissue mechanics. While most well-established tools probing mechanical properties require an invasive sample preparation, confocal Brillouin microscopy captures mechanical parameters optically with high resolution in a contact-free and label-free fashion. In this work, we took advantage of this tool and the transparency of the highly regenerative axolotl to probe its mechanical properties in vivo for the first time. We mapped the Brillouin frequency shift with high resolution in developing limbs and regenerating digits, the most studied structures in the axolotl. We detected a gradual increase in the cartilage Brillouin frequency shift, suggesting decreasing tissue compressibility during both development and regeneration. Moreover, we were able to correlate such an increase with the regeneration stage, which was undetected with fluorescence microscopy imaging. The present work evidences the potential of Brillouin microscopy to unravel the mechanical changes occurring in vivo in axolotls, setting the basis to apply this technique in the growing field of epimorphic regeneration.


Asunto(s)
Ambystoma mexicanum , Animales , Microscopía Confocal/métodos
19.
Sci Rep ; 12(1): 7880, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35551247

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has evolved to have a wide range of hosts, including non-human primates, wild and domestic animals. The ACE2 protein has a high level of conservation and is the common receptor invertebrate species for a viral infection to occur; this receptor could give rise to anthroponotic events. This article describes the first event of symptomatic transmission in Latin America from a human to a dog by the B.1.625 lineage of SARS-CoV-2. We found 21 shared mutations in the complete genomes of viral sequences from owners and dogs. Further phylogenetic and molecular analysis showed that 100% co-localization of the clade helps to understand human-animal transmission. Prediction of the Spike protein structure of the sequenced virus and docking analyzes showed that the E484K mutation in the receptor-binding domain (RBD) could contribute to the viral affinity of dACE2. Therefore, close contact between SARS-CoV-2-infected humans and pets should be avoided to prevent the emergence of novel mutations of public health importance from anthroponotic events.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Animales Domésticos/metabolismo , Colombia/epidemiología , Perros , Humanos , Mutación , Pandemias , Filogenia , Unión Proteica , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo
20.
Mem Inst Oswaldo Cruz ; 117: e210375, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35544862

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus of zoonotic origin that can bind to ACE2 receptors on the cells of many wild and domestic mammals. Studies have shown that the virus can circulate among animals mutate, lead to animal-to-human zoonotic jump, and further onward spread between humans. Infection in pets is unusual, and there are few human-to-pet transmission reports worldwide. OBJECTIVE: To describe the SARS-CoV-2 infection in a domestic animal in Córdoba, Colombian Caribbean region. METHODS: A cross-sectional molecular surveillance study was carried out, oral and rectal swabs were taken from cats and dogs living with people diagnosed with coronavirus disease 2019 (COVID-19). RESULTS: SARS-CoV-2 was found in a cat living with a person with COVID-19. Genome sequencing showed that the B.1.111 lineage caused the infection in the cat. The owner's sample could not be sequenced. The lineage is predominant in Colombia, and this variant is characterised by the presence of the D614D and Q57H mutation. CONCLUSION: The present work is the first report of an infected cat with SARS-CoV-2 with whole-genome sequencing in Colombia. It highlights the importance of detecting SARS-CoV-2 mutations that could promote the transmissibility of this new coronavirus. There is still a significant information gap on human-to-cat-to-human infection; we encourage self-isolation measures between COVID-19 patients and companion animals. The findings of this study give a preliminary view of the current panorama of SARS-CoV-2 infection in animals in Colombia.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , COVID-19/diagnóstico , COVID-19/veterinaria , Gatos , Colombia/epidemiología , Estudios Transversales , Perros , Humanos , Mamíferos/genética , SARS-CoV-2/genética , Secuenciación Completa del Genoma
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