Humberto Alejandro Nati-Castillo

Dr. Humberto Alejandro Nati-Castillo

orcid

Research Focus & Metrics

Academic Career Length

9Years (2018-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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19 June 2025 in Cells
Verified
Journal Article
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Jhan Sebastian Saavedra T.Jhan Sebastian Saavedra T.
Jhan Sebastian Saavedra T.
MPMaría Virginia Pinzón-Fernández
María Virginia Pinzón-Fernández
MPMartin Ocampo Posada
Martin Ocampo Posada
HNHumberto Alejandro Nati-Castillo
Humberto Alejandro Nati-Castillo
LHLaura Alejandra Jiménez Hincapié
Laura Alejandra Jiménez Hincapié
Juan S. Izquierdo-CondoyJuan S. Izquierdo-Condoy
Juan S. Izquierdo-Condoy
Sepsis is a life-threatening syndrome characterized by a dysregulated immune response to infection, frequently leading to multiorgan failure and high mortality. Inflammasomes—cytosolic multiprotein complexes of the innate immune system—serve as critical platforms for sensing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). Key sensors such as NLRP3, AIM2, and IFI16 initiate caspase-1 activation, IL-1β and IL-18 maturation, and gasdermin D–mediated pyroptosis. In sepsis, excessive inflammasome activation drives oxidative stress, endothelial dysfunction, immunothrombosis, and immune exhaustion. This maladaptive cascade is further aggravated by the release of DAMPs and procoagulant factors, compromising vascular integrity and immune homeostasis. Prolonged activation contributes to immunoparalysis, lymphopenia, and increased susceptibility to secondary infections. Inflammasome signaling also intersects with necroptosis and ferroptosis, amplifying systemic inflammation and tissue injury. Additionally, various pathogens exploit immune evasion strategies to modulate inflammasome responses and enhance virulence. Therapeutic interventions under investigation include selective NLRP3 inhibitors, IL-1 blockers, gasdermin D antagonists, and extracorporeal cytokine hemoadsorption. Emerging approaches emphasize biomarker-guided immunomodulation to achieve personalized therapy. While preclinical studies have shown promising results, clinical translation remains limited. Targeting inflammasomes may offer a path toward precision immunotherapy in sepsis, with potential to reduce organ dysfunction and improve survival.

2 September 2025 in Biomedicines
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Journal Article
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Jhan Sebastian Saavedra T.Jhan Sebastian Saavedra T.
Jhan Sebastian Saavedra T.
MPMaría Virginia Pinzón-Fernández
María Virginia Pinzón-Fernández
HNHumberto Alejandro Nati-Castillo
Humberto Alejandro Nati-Castillo
VCValentina Cadena Correa
Valentina Cadena Correa
LMLuis Carlos López Montilla
Luis Carlos López Montilla
Juan S. Izquierdo-CondoyJuan S. Izquierdo-Condoy
Juan S. Izquierdo-Condoy
Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection. It follows a dynamic course in which early hyperinflammation coexists and overlaps with progressive immune suppression, a process best described as immunodynamic disruption. Key mechanisms include extensive lymphocyte death, expansion of regulatory T cells, impaired antigen presentation, and persistent activation of inhibitory checkpoints such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4). These changes reduce immune competence and increase vulnerability to secondary infections. Clinically, reduced expression of Human Leukocyte Antigen–DR (HLA-DR) on monocytes and persistent lymphopenia have emerged as robust biomarkers for patient stratification and timing of immunomodulatory therapies. Beyond the acute phase, many survivors do not achieve full immune recovery but instead develop a Persistent Immune Remnant, defined as long-lasting immune, metabolic, and endothelial dysfunction despite apparent clinical resolution. Recognizing PIR emphasizes the need for long-term monitoring and biomarker-guided interventions to restore immune balance. To integrate these observations, we propose the SIMMP–Sepsis model (Sepsis-Associated Persistent Multiorgan Immunometabolic Syndrome), which links molecular dysfunction to clinical trajectories and provides a framework for developing precision immunotherapies. This perspective reframes sepsis not only as an acute crisis but also as a chronic immunometabolic syndrome, where survival marks the beginning of active immune restoration.

Verified
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NGNelson López Garzón
Nelson López Garzón
MPMaría Virginia Pinzón-Fernández
María Virginia Pinzón-Fernández
Jhan Sebastian Saavedra T.Jhan Sebastian Saavedra T.
Jhan Sebastian Saavedra T.
HNHumberto Alejandro Nati-Castillo
Humberto Alejandro Nati-Castillo
Marlon Armando Arias IntriagoMarlon Armando Arias Intriago
Marlon Armando Arias Intriago
Juan S. Izquierdo-CondoyJuan S. Izquierdo-Condoy
Juan S. Izquierdo-Condoy
Microgravity, defined by minimal gravitational forces, represents a unique environment that profoundly influences biological systems, including human cells. This review examines the effects of microgravity on biological processes and their implications for human health. Microgravity significantly impacts the immune system by disrupting key mechanisms, such as T cell activation, cytokine production, and macrophage differentiation, leading to increased susceptibility to infections. In cancer biology, it promotes the formation of spheroids in cancer stem cells and thyroid cancer cells, which closely mimic in vivo tumor dynamics, providing novel insights for oncology research. Additionally, microgravity enhances tissue regeneration by modulating critical pathways, including Hippo and PI3K-Akt, thereby improving stem cell differentiation into hematopoietic and cardiomyocyte lineages. At the organ level, microgravity induces notable changes in hepatic metabolism, endothelial function, and bone mechanotransduction, contributing to lipid dysregulation, vascular remodeling, and accelerated bone loss. Notably, cardiomyocytes derived from human pluripotent stem cells and cultured under microgravity exhibit enhanced mitochondrial biogenesis, improved calcium handling, and advanced structural maturation, including increased sarcomere length and nuclear eccentricity. These advancements enable the development of functional cardiomyocytes, presenting promising therapeutic opportunities for treating cardiac diseases, such as myocardial infarctions. These findings underscore the dual implications of microgravity for space medicine and terrestrial health. They highlight its potential to drive advances in regenerative therapies, oncology, and immunological interventions. Continued research into the biological effects of microgravity is essential for protecting astronaut health during prolonged space missions and fostering biomedical innovations with transformative applications on Earth.

10 February 2025 in Journal of Medical Internet Research
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Journal Article
Open access
Juan S. Izquierdo-CondoyJuan S. Izquierdo-Condoy
Juan S. Izquierdo-Condoy
Clara PazClara Paz
Clara Paz
HNHumberto Alejandro Nati-Castillo
Humberto Alejandro Nati-Castillo
RGRicardo Gollini-Mihalopoulos
Ricardo Gollini-Mihalopoulos
TRTelmo Raul Aveiro Robalo
Telmo Raul Aveiro Robalo
EOEsteban Ortiz-Prado
Esteban Ortiz-Prado
Background: The ubiquitous use of mobile phones among medical students has been linked to potential health consequences, including poor sleep quality. Objective: This study investigates the prevalence of mobile phone addiction and its association with sleep quality among medical students across 6 Latin American countries. Methods: A descriptive, cross-sectional, multicenter study was conducted between December 2023 and March 2024 using a self-administered online survey. The survey incorporated the Mobile Phone Addiction Scale and the Pittsburgh Sleep Quality Index to evaluate mobile phone addiction and sleep quality among 1677 medical students. A multiple regression model was applied to analyze the relationship between mobile phone addiction and poor sleep quality, adjusting for sex, age, and educational level to ensure robust results. Results: Mobile phone addiction was identified in 32.5% (545/1677) of participants, with significant differences across countries. The overall mean Pittsburgh Sleep Quality Index score was 7.26, indicating poor sleep quality. Multiple regression analysis revealed a strong association between mobile phone addiction and poor sleep, controlled for demographic variables (β=1.4, 95% CI 1.05-1.74). Conclusions: This study underscores a significant prevalence of mobile phone addiction among medical students and its detrimental association with sleep quality in Latin America. The findings advocate for the need to address mobile phone usage to mitigate its negative implications on student health and academic performance. Strategies to enhance digital literacy and promote healthier usage habits could benefit medical education and student well-being.

1 March 2023 in Advances in Medical Education and Practice
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Journal Article
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JIJuan S Izquierdo-Condoy
Juan S Izquierdo-Condoy
MMMiguel Angel Montiel-Alfonso
Miguel Angel Montiel-Alfonso
HNHumberto Alejandro Nati-Castillo
Humberto Alejandro Nati-Castillo
RSRuth Saucedo
Ruth Saucedo
Damary S. Jaramillo-AguilarDamary S. Jaramillo-Aguilar
Damary S. Jaramillo-Aguilar
EOEsteban Ortiz-Prado
Esteban Ortiz-Prado
Purpose: The objective of this study was to describe the level of knowledge, perceptions, and practices in relation to risks and disasters in medical schools in Latin America and the Caribbean. Participants and Methods: Multicenter, observational, analytical, non-probabilistic convenience sample study with 2546 medical students in 9 countries of Latin America and the Caribbean. An online survey was conducted between October 2020 and November 2020, using an instrument validated in each country to assess knowledge, perceptions, and practices regarding risk and disaster prevention measures. Frequencies, percentages, mean and standard deviation (SD) were used for descriptive analysis. Differences resulting from the relationship between the variables studied and the level of knowledge were obtained using the Chi-square test. P-value < 0.05 was accepted as statistically significant for all analyses. Results: The highest proportion of responses came from women, third-semester students, and those studying in public universities. Students from Colombia and Honduras had the highest percentage of high levels of knowledge about disasters, while Peruvian students had the highest percentage of low levels of knowledge. Women and students from public universities showed a higher proportion of high levels of knowledge. 52.7% considered that they live in a country with a medium risk of natural disasters, while 91.2% said that Latin American and Caribbean countries are not prepared to face natural disasters. Only 43.6% believe they are prepared to help in the event of a natural disaster. Conclusion: Most of medical students from Latin America and Latin America and the Caribbean have high and medium level of knowledge in risks and disasters. However, the implementation of disaster training programs for medical students has the potential to improve the preparedness, knowledge, and skills that are important for medical personnel to improve their self-confidence, and their ability to respond, resulting in more effective systems.

9 March 2025 in Gut Pathogens
Verified
Journal Article
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JTJessica Triviño-Valencia
Jessica Triviño-Valencia
HNHumberto Alejandro Nati-Castillo
Humberto Alejandro Nati-Castillo
NCNancy Yhomara Cabeza
Nancy Yhomara Cabeza
FLFabiana Lora-Suarez
Fabiana Lora-Suarez
Jorge Enrique Gomez-MarinJorge Enrique Gomez-Marin
Jorge Enrique Gomez-Marin
There are no reports with molecular confirmation of Cryptosporidium spp. and Cyclospora spp. in children consulting the emergency service due to diarrhoea in Colombia. A descriptive study was performed on 137 children who visited the Hospital San Juan de Dios Emergency Service in Armenia between April 1 and 31, 2022. Questionnaires and sampling were performed to identify parasites in the faecal samples. Fresh preparations were prepared with 1% iodine, and a modified Ziehl-Neelsen stain was used to identify pathogenic intestinal protozoa (Cryptosporidium spp. and Cyclospora spp.). PCR and sequencing of positive samples were performed to confirm infection. The prevalence of Cryptosporidium spp. infection in children was 19,7%, and that of Cyclospora spp. was 10,9%. 59,2% of the children with cryptosporidiosis and 66,6% of the children with cyclosporiasis were hospitalized. PCR for Cryptosporidium spp. was positive in six of 28 (21%) samples and for Cyclospora in 11 of 15 (73%) samples. Cyclospora spp. SSU rRNA DNA sequences clustered 10 samples nearest to lineage A, two with lineage B, and one with lineage C. Cryptosporidiosis and cyclosporiasis are common in children with acute diarrhoea when consulting emergency services, and their search should be performed systematically.