Compuestos bioactivos de canela y su efecto en la disminución del síndrome metabólico: revisión sistemática / Bioactive compounds of cinnamon and their effect on decreasing metabolic syndrome: systematic review

Introducción. El síndrome metabólico (SM) aumenta el ingreso hospitalario y el riesgo de desarrollar COVID-19, los fármacos utilizados para su tratamiento ocasionan efectos secundarios por lo que se ha optado por la búsqueda de alternativas terapéuticas a base de compuestos bioactivos contenidos en plantas medicinales. La canela se utiliza como agente terapéutico debido a sus propiedades comprobadas con diversos mecanismos de acción reportados en el tratamiento de varias patologías. Objetivo. Documentar los estudios in vitro, in vivo, estudios clínicos y los mecanismos de acción reportados del efecto de la administración de extractos y polvo de canela en las comorbilidades relacionadas con el SM. Materiales y métodos. Revisión sistemàtica de artículos en bases de datos electrónicas, incluyendo estudios de canela en polvo, extractos acuosos, de acetato de etilo y metanol de la corteza de canela, período de 5 años, excluyendo todo artículo relacionado a su efecto antimicrobiano, antifúngico y aceite de canela. Resultados. Las evidencias de los principales compuestos bioactivos contenidos en la canela validan su potencial en el tratamiento de enfermedades relacionadas al SM, con limitados estudios que indagan en los mecanismos de acción correspondientes a sus actividades biológicas. Conclusiones. Las evidencias de las investigaciones validan su potencial en el tratamiento de estas patologías, debido a sus principales compuestos bioactivos: cinamaldehído, transcinamaldehído, ácido cinámico, eugenol y, antioxidantes del tipo proantocianidinas A y flavonoides, los cuales participan en diversos mecanismos de acción que activan e inhiben enzimas, con efecto hipoglucemiante (quinasa y fosfatasa), antiobesogénico (UPC1), antiinflamatorio (NOS y COX), hipolipemiante (HMG-CoA) y antihipertensivo (ECA)(AU)

Introduction. Metabolic syndrome (MS) increases hospital admission and the risk of developing COVID-19. Due to the side effects caused by the drugs used for its treatment, the search for therapeutic alternatives based on bioactive compounds contained in medicinal plants has been chosen. Cinnamon is used as a therapeutic agent due to its proven properties with various mechanisms of action reported in the treatment of various pathologies. Objective. To document the in vitro and in vivo studies, clinical studies and the mechanisms of action reported on the effect of the administration of cinnamon extracts and powder on comorbidities related to MS. Materials and methods. Systematic review of articles in electronic databases, including studies of cinnamon powder, aqueous extracts, ethyl acetate and methanol from cinnamon bark, over a period of 5 years, excluding all those articles related to its antimicrobial, antifungal and antimicrobial effect. cinnamon oil. Results. The evidence of the main bioactive compounds contained in cinnamon validates its potential in the treatment of diseases related to MS, with limited studies that investigate the mechanisms of action corresponding to its biological activities. Conclusions. Research evidence validates its potential in the treatment of these pathologies, due to its main bioactive compounds: cinnamaldehyde, transcinnamaldehyde, cinnamic acid, eugenol, and antioxidants of the proanthocyanidin A type and flavonoids, which participate in various mechanisms of action that activate and they inhibit enzymes, with hypoglycemic (kinase and phosphatase), antiobesogenic (UPC1), anti-inflammatory (NOS and COX), lipid-lowering (HMG-CoA) and antihypertensive (ACE) effects(AU)

Use of Radioisotope Ratios of Lead for the Identification of Historical Sources of Soil Lead Contamination in Santa Ana, California.

Lead (Pb) is an environmental neurotoxicant that has been associated with a wide range of adverse health conditions, and which originates from both anthropogenic and natural sources. In California, the city of Santa Ana represents an urban environment where elevated soil lead levels have been recently reported across many disadvantaged communities. In this study, we pursued a community-engaged research approach through which trained "citizen scientists" from the surrounding Santa Ana community volunteered to collect soil samples for heavy metal testing, a subset of which (n = 129) were subjected to Pb isotopic analysis in order to help determine whether contamination could be traced to specific and/or anthropogenic sources. Results showed the average 206Pb/204Pb ratio in shallow soil samples to be lower on average than deep samples, consistent with shallow samples being more likely to have experienced historical anthropogenic contamination. An analysis of soil Pb enrichment factors (EFs) demonstrated a strong positive correlation with lead concentrations, reinforcing the likelihood of elevated lead levels being due to anthropogenic activity, while EF values plotted against 206Pb/204Pb pointed to traffic-related emissions as a likely source. 206Pb/204Pb ratios for samples collected near historical urban areas were lower than the averages for samples collected elsewhere, and plots of 206Pb/204Pb against 206Pb/207 showed historical areas to exhibit very similar patterns to those of shallow samples, again suggesting lead contamination to be anthropogenic in origin, and likely from vehicle emissions. This study lends added weight to the need for health officials and elected representatives to respond to community concerns and the need for soil remediation to equitably protect the public.

Use of historical mapping to understand sources of soil-lead contamination: Case study of Santa Ana, CA.

This paper investigates the historical sources of soil-lead contamination in Santa Ana, California. Even though dangerous levels of soil-lead have been found in a wide variety of communities across the United States, public health institutions lack clarity on the historical origins of these crises. This study uses geo-spatial data collected through archival research to estimate the impact of two potential sources of lead contamination in the past -- lead-paint and leaded gasoline. It examines, through a combination of statistical and historical methods, the association between lead concentrations in contemporary soil samples and patterns in the evolution of the city's physical features, such as the growth of urbanized areas and the historical flow of traffic. We emphasize the value of historical data collected through archival research for understanding the sources of environmental lead, particularly leaded gasoline, which our study found to be the most likely and most prominent contributor to soil-lead in Santa Ana's environment. This research contributes to environmental-justice advocacy efforts to reframe lead poisoning as a systemic environmental issue and outlines the path forward to community-level remediation strategies.

Orange County, California COVID-19 Vaccine Equity Best Practices Checklist: A Community-Centered Call to Action for Equitable Vaccination Practices.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has exacerbated longstanding inequities throughout the United States, disproportionately concentrating adverse social, economic, and health-related outcomes among low-income communities and communities of color. Inequitable distribution, prioritization, and uptake of COVID-19 vaccines due to systemic and organizational barriers add to these disproportionate impacts across the United States. Similar patterns have been observed within Orange County, California (OC). Methods: In response to COVID-19 vaccine inequities unfolding locally, the Orange County Health Equity COVID-19 community-academic partnership generated a tool to guide a more equitable vaccine approach. Contents of the OC vaccine equity best practices checklist emerged through synthesis of community-level knowledge about vaccine inequities, literature regarding equitable vaccination considerations, and practice-based health equity guides. We combined into a memo: the checklist, a written explanation of its goals and origins, and three specific action steps meant to further strengthen the focus on vaccine equity. The memo was endorsed by partnership members and distributed to county officials. Discussion: Since the initial composition of the checklist, the local vaccine distribution approach has shifted, suggesting that equitable pandemic responses require continual re-evaluation of local needs and adjustments to recommendations as new information emerges. To understand and address structural changes needed to reduce racial and socioeconomic inequities exacerbated by the pandemic, authentic partnerships between community, academic, and public health practice partners are necessary. Conclusion: As we face continued COVID-19 vaccine rollout, booster vaccination, and future pandemic challenges, community knowledge and public health literature should be integrated to inform similar equity-driven strategic actions.

Risk assessment of soil heavy metal contamination at the census tract level in the city of Santa Ana, CA: implications for health and environmental justice.

(1) Background: exposure to heavy metals is associated with adverse health effects and disproportionately impacts low-income communities and communities of color. We carried out a community-based participatory research study to examine the distribution of heavy metal concentrations in the soil and social vulnerabilities to soil heavy metal exposures across Census tracts in Santa Ana, CA. (2) Methods: soil samples (n = 1528) of eight heavy metals including lead (Pb), arsenic (As), manganese (Mn), chromium (Cr), nickel (Ni), copper (Cu), cadmium (Cd), and zinc (Zn) were collected in 2018 across Santa Ana, CA, at a high spatial resolution and analyzed using XRF analysis. Metal concentrations were mapped out and American Community Survey data was utilized to assess metals throughout Census tracts in terms of social and economic variables. Risk assessment was conducted to evaluate carcinogenic and non-carcinogenic risk. (3) Results: concentrations of soil metals varied according to landuse type and socioeconomic factors. Census tracts where the median household income was under $50 000 had 390%, 92.9%, 56.6%, and 54.3% higher Pb, Zn, Cd, and As concentrations compared to high-income counterparts. All Census tracts in Santa Ana showed hazard index >1, implying the potential for non-carcinogenic health effects, and nearly all Census tracts showed a cancer risk above 10-4, implying a greater than acceptable risk. Risk was predominantly driven by childhood exposure. (4) Conclusions: findings inform initiatives related to environmental justice and highlight subpopulations at elevated risk of heavy metal exposure, in turn underscoring the need for community-driven recommendations for policies and other actions to remediate soil contamination and protect the health of residents.

Social and spatial distribution of soil lead concentrations in the City of Santa Ana, California: Implications for health inequities.

BACKGROUND: Lead (Pb) exposure is a problem that disproportionately impacts low-income communities and communities of color. We applied a community-based participatory research approach to assess the distribution of soil Pb concentrations and related social vulnerabilities across Census tracts in Santa Ana, CA. METHODS: Soil Pb samples (n = 1528) were collected by the ¡Plo-NO! Santa Ana! Lead-Free Santa Ana! partnership in 2018 across Santa Ana, CA, at a high spatial resolution and measured using XRF analysis. Pb concentrations were mapped and spatial interpolation was conducted to generate a continuous smoothed map of soil Pb concentrations across the city. American Community Survey data was used to examine Pb across Census tracts based on social and economic factors, and to allow for the development of a Cumulative Risk Index to identify areas at high risk of health impacts. RESULTS: Soil Pb concentrations varied by landuse type and socioeconomic factors. Census tracts with a median household income below $50,000 had over five times higher soil Pb concentrations than high-income Census tracts. Soil samples collected in tertiles with the highest percent children, residents without health insurance, renter-occupied housing units, and lowest percent college educated residents had 90.0%, 96.1%, 75.2%, and 87.0% higher Pb concentrations on average, respectively, compared to their counterparts. Overall, 52.7% of residential samples had Pb concentrations in excess of the 80 ppm California EPA recommendation, and 11 Census tracts were characterized as high risk according to our Cumulative Risk Index. DISCUSSION: This study underscores the need for precautionary measures relating to disturbances of the soil, particularly for areas where children play outside, given children's higher absorption of lead. It also informs environmental justice initiatives and identifies vulnerable subpopulations at greater risk of Pb exposure, thus warranting community-driven recommendations for policies and initiatives to remediate soil Pb and protect public health and health equity.

Cardiovascular Disease Risk in Children With Kidney Disease.

Cardiovascular disease is a major cause of death in individuals diagnosed with kidney disease during childhood. Children with kidney disease often incur a significant cardiovascular burden that leads to increased risk for cardiovascular disease. Evidence has shown that children with kidney disease, including chronic kidney disease, dialysis, kidney transplantation, and nephrotic syndrome, develop abnormalities in cardiovascular markers such as hypertension, dyslipidemia, left ventricular hypertrophy, left ventricular dysfunction, atherosclerosis, and aortic stiffness. Early identification of modifiable risk factors and treatment may lead to a decrease of long-term cardiovascular morbidity and mortality, but evidence in this population is lacking.

Oligomerization of the chitin synthase Chs3 is monitored at the Golgi and affects its endocytic recycling.

Chs3, the catalytic subunit of chitin synthase III in Saccharomyces cerevisiae, is a complex polytopic membrane protein whose plasma membrane expression is tightly controlled: export from the ER requires interaction with Chs7; exit from the Golgi is dependent on the exomer complex, and precise bud neck localization relies on endocytosis. Moreover, Chs3 is efficiently recycled from endosomes to the TGN in an AP-1-dependent manner. Here we show that the export of Chs3 requires the cargo receptor Erv14, in a step that is independent of Chs7. Chs3 oligomerized in the ER through its N-terminal cytosolic region. However, the truncated (Δ126)Chs3 was still exported by Erv14, but was sent back from the Golgi to the ER in a COPI- and Rer1-dependent manner. A subset of the oligomerization-deficient Chs3 proteins evaded Golgi quality control and reached the plasma membrane, where they were enzymatically active but poorly endocytosed. This resulted in high CSIII levels, but calcofluor white resistance, explained by the reduced intercalation of calcofluor white between nascent chitin fibres. Our data show that the oligomerization of Chs3 through its N-terminus is essential for proper protein trafficking and chitin synthesis and is therefore monitored intracellularly.

Neck compartmentalization as the molecular basis for the different endocytic behaviour of Chs3 during budding or hyperpolarized growth in yeast cells.

Yeast cells normally grow by budding, but under certain specific conditions they are also able to grow in hyperpolarized forms reminiscent of hyphal growth. During vegetative growth, the synthesis of the septum that physically separates yeast cells during cytokinesis depends on the correct assembly of the septin ring. Septins and actin patches are assembled at the neck, forming two concentric rings where the actin patch ring occupies the external-most part. This specific positioning defines a plasma membrane region at the neck from which other lateral membrane compartments are excluded. In this scenario, correct assembly of the chitin ring is dependent on the anchoring of Chs3 to the septin ring through Chs4. The anchoring of Chs3 to septins through Chs4 prevents the arrival of this protein at endocytic sites, thus reducing the endocytosis of Chs3. This allows an equilibrium to be set up between the antero- and retrograde transport of Chs3, facilitating the synthesis of the chitin ring at the neck. In contrast, hyperpolarized growth is characterized by a reduced endocytic turnover of Chs3, which in turn lead to the accumulation of Chs3 at the plasma membrane and a concomitant increase in chitin synthesis.

Slt2 and Rim101 contribute independently to the correct assembly of the chitin ring at the budding yeast neck in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the simultaneous absence of Slt2 and Rim101 prevents growth in nonosmotically stabilized media (F. Castrejon et al., Eukaryot. Cell 5:507-517, 2006). The double mutant slt2Delta rim101Delta displays altered chitin rings, together with a significant reduction in the overall levels of chitin. Cultures of this mutant lyse upon transfer to nonosmotically stabilized media, mostly through the bud, and such lysis is partially prevented by deletion of the chitinase gene (CTS1). Growth of the slt2Delta rim101Delta double mutant was restored by the overexpression of the GFA1 or CCT7 genes, which code for two biologically unrelated proteins. Further characterization of the mutant and its suppressors indicated that both Slt2 and Rim101 were independently required for the correct assembly of the septum machinery and that their concomitant absence reduced Chs3 accumulation at the neck, leading to lower levels of chitin. GFA1 overexpression, as well as the addition of glucosamine to the growth medium, specifically suppressed the growth defects by activating chitin synthesis at the neck and restoring the normal assembly of the chitin ring. In contrast, overexpression of CCT7, a Cct chaperonin subunit, alleviated the defect in the septum machinery without affecting chitin synthesis. Both suppressors thus act by reducing neck fragility through different mechanisms and allow growth in nonstabilized media. This work reports new roles for Slt2 and Rim101 in septum formation in budding yeast and confirms the homeostatic role of the chitin ring in the maintenance of neck integrity during cell division.

Chitin synthase III requires Chs4p-dependent translocation of Chs3p into the plasma membrane.

In Saccharomyces cerevisiae, Chs4p is required for chitin synthase III (CSIII) activity and hence for chitin synthesis. This protein is transported in vesicles in a polarized fashion independently of the other Chs proteins. Its association with membranes depends not only on prenylation, but also on its interaction with other proteins, mainly Chs3p, which is the catalytic subunit of CSIII and is able to properly direct Chs4p to the bud neck in the absence of prenylation. Chs4p is present in functionally limiting amounts and its overexpression increases Chs3p accumulation at the plasma membrane with a concomitant increase in chitin synthesis. In the absence of Chs4p, Chs3p is delivered to the plasma membrane but fails to accumulate there because it is rapidly endocytosed and accumulates in intracellular vesicles. A blockade of endocytosis stops Chs3p internalization, triggering a significant increase in chitin synthesis. This blockade is independent of Chs4p function, allowing the accumulation of Chs3p at the plasma membrane even in the chs4Delta mutant. However, the absence of Chs4p renders CSIII functionally inactive, independently of Chs3p accumulation at the plasma membrane. Chs4p thus promotes Chs3p translocation into the plasma membrane in a stable and active form. Proper CSIII turnover is maintained through the endocytic internalization of Chs3p.