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1.
Life (Basel) ; 14(4)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38672763

ABSTRACT

The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-Like Family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which revealed significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~90 potential genes that participate in the regulation of the hypertrophic environment (or CVDs' Environment). Also, the GO analysis showed that genes containing the motif CACCC were enriched for multiple CVDs; in combination with STRING analysis, these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

2.
IJID Reg ; 9: 72-79, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37928801

ABSTRACT

Objectives: This work provides an overview of young children's (aged 0-9) infectious diseases epidemiology, by exploring the link between various comorbid conditions, COVID-19, and death rate. Methods: Public data on hospitalized young children was obtained from national databases of the Mexican health care system from 2020-2022. Data included age, year of entry, gender, the time between admission to death (hospitalization time), date of death, comorbidities, and admissions to the intensive care unit. Children were separated into age groups and frequencies were calculated. Binary regression models were developed to determine the correlation of comorbidities and COVID-19 to death as calculated by odds ratios (OR). Results: From 2020-2022, there were 11,815 hospitalizations among young children, of which 15.98% were due to COVID-19, 2.55% of hospitalizations resulted in fatalities from which 32.45% of deaths were COVID-19 related. The highest case-calculated fatality ratio of COVID-19 infected young children was estimated at 7.04% by early 2020, but dropped to 2.11% by the end of the second semester of 2022. The most frequent comorbidities associated with their hospitalization and death for the general population were intubation (OR: 17.967), pneumonia (OR: 2.263), diabetes (OR: 7.301), cardiovascular diseases (OR: 1.528) and COVID-19 (OR: 261). For the COVID-19-positive group, the most impactful comorbidities were intubation (OR: 20.232), pneumonia (OR: 3.057), and diabetes (OR: 12.824). Conclusion: Children's hospitalizations and deaths were common during the pandemic; wherein major comorbidities played an important role. Therefore, effective comorbidity management and vaccination programs are essential to reduce hospitalizations and deaths among young children.

3.
Foods ; 12(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37685194

ABSTRACT

The high rate of deaths around the world from noncommunicable diseases (NCDs) (70%) is a consequence of a poor diet lacking in nutrients and is linked to lifestyle and environmental conditions that together trigger predisposing factors. NCDs have increased 9.8% of public health spending worldwide, which has been increasing since 2000. Hence, international organizations such as the WHO, the Pan American Health Organization, and the Food and Agriculture Organization of the United Nations have been developing strategic plans to implement government and economic policies to strengthen programs in favor of food security and nutrition. A systematic review is presented to document an analysis of the origin and characteristics of obesity, cardiovascular disease, chronic respiratory diseases, diabetes, and cancers affecting a large part of the world's population. This review proposes a scientifically based report of functional foods including fruits, vegetables, grains, and plants, and how their bioactive compounds called nutraceuticals-when consumed as part of a diet-benefit in the prevention and treatment of NCDs from an early age. Multifactorial aspects of NCDs, such as culture and eating habits, are limitations to consider from the clinical, nutritional, and biochemical points of view of everyone who suffers from them.

4.
Brain Sci ; 13(3)2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36979323

ABSTRACT

Coronavirus disease (COVID-19) represents one of the greatest challenges to public health in modern history. As the disease continues to spread globally, medical and allied healthcare professionals have become one of the most affected sectors. Stress and anxiety are indirect effects of the COVID-19 pandemic. Therefore, it is paramount to understand and categorize their perceived levels of stress, as it can be a detonating factor leading to mental illness. Here, we propose a computer-based method to better understand stress in healthcare workers facing COVID-19 at the beginning of the pandemic. We based our study on a representative sample of healthcare professionals attending to COVID-19 patients in the northeast region of Mexico, at the beginning of the pandemic. We used a machine learning classification algorithm to obtain a visualization model to analyze perceived stress. The C5.0 decision tree algorithm was used to study datasets. We carried out an initial preprocessing statistical analysis for a group of 101 participants. We performed chi-square tests for all questions, individually, in order to validate stress level calculation (p < 0.05) and a calculated Cronbach's alpha of 0.94 and McDonald's omega of 0.95, demonstrating good internal consistency in the dataset. The obtained model failed to classify only 6 out of the 101, missing two cases for mild, three for moderate and one for severe (accuracy of 94.1%). We performed statistical correlation analysis to ensure integrity of the method. In addition, based on the decision tree model, we concluded that severe stress cases can be related mostly to high levels of xenophobia and compulsive stress. Thus, showing that applied machine learning algorithms represent valuable tools in the assessment of perceived stress, which can potentially be adapted to other areas of the medical field.

5.
Life (Basel) ; 13(2)2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36836777

ABSTRACT

Krüppel-like factors (KLFs) are a set of DNA-binding proteins belonging to a family of zinc-finger transcription factors, which have been associated with many biological processes related to the activation or repression of genes, inducing cell growth, differentiation, and death, and the development and maintenance of tissues. In response to metabolic alterations caused by disease and stress, the heart will undergo cardiac remodeling, leading to cardiovascular diseases (CVDs). KLFs are among the transcriptional factors that take control of many physiological and, in this case, pathophysiological processes of CVD. KLFs seem to be associated with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss of functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of the differentiation of cardiac myofibroblasts or a modified fatty acid oxidation related to the formation of a dilated cardiomyopathy, myocardial infarctions, left ventricular hypertrophy, and diabetic cardiomyopathies. In this review, we describe the importance of KLFs in cardiovascular diseases such as atherosclerosis, myocardial infarction, left ventricle hypertrophy, stroke, diabetic cardiomyopathy, and congenital heart diseases. We further discuss microRNAs that have been involved in certain regulatory loops of KLFs as they may act as critical in CVDs.

6.
Front Public Health ; 10: 1008565, 2022.
Article in English | MEDLINE | ID: mdl-36438268

ABSTRACT

Cardiovascular diseases (CVDs) continue to be the leading cause of death worldwide. Over the past couple of years and with the surge of the COVID-19 pandemic, mortality from CVDs has been slightly overshadowed by those due to COVID-19, although it was during the peak of the pandemic. In the present study, patients with CVDs (CVDs; n = 41,883) were analyzed to determine which comorbidities had the largest impact on overall patient mortality due to their association with both diseases (n = 3,637). Obesity, hypertension, and diabetes worsen health in patients diagnosed positive for COVID-19. Hence, they were included in the overview of all patients with CVD. Our findings showed that 1,697 deaths were attributable to diabetes (p < 0.001) and 987 deaths to obesity (p < 0.001). Lastly, 2,499 deaths were attributable to hypertension (p < 0.001). Using logistic regression modeling, we found that diabetes (OR: 1.744, p < 0.001) and hypertension (OR: 2.179, p < 0.001) significantly affected the mortality rate of patients. Hence, having a CVD diagnosis, with hypertension and/or diabetes, seems to increase the likelihood of complications, leading to death in patients diagnosed positive for COVID-19.


Subject(s)
COVID-19 , Cardiovascular Diseases , Diabetes Mellitus , Hypertension , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cross-Sectional Studies , COVID-19/epidemiology , Retrospective Studies , Pandemics , Hypertension/epidemiology , Diabetes Mellitus/epidemiology , Obesity/epidemiology
7.
Int J Mol Sci ; 23(17)2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36077276

ABSTRACT

Articular cartilage is a highly organized tissue that provides remarkable load-bearing and low friction properties, allowing for smooth movement of diarthrodial joints; however, due to the avascular, aneural, and non-lymphatic characteristics of cartilage, joint cartilage has self-regeneration and repair limitations. Cartilage tissue engineering is a promising alternative for chondral defect repair. It proposes models that mimic natural tissue structure through the use of cells, scaffolds, and signaling factors to repair, replace, maintain, or improve the specific function of the tissue. In chondral tissue engineering, fibrin is a biocompatible biomaterial suitable for cell growth and differentiation with adequate properties to regenerate damaged cartilage. Additionally, its mechanical, biological, and physical properties can be enhanced by combining it with other materials or biological components. This review addresses the biological, physical, and mechanical properties of fibrin as a biomaterial for cartilage tissue engineering and as an element to enhance the regeneration or repair of chondral lesions.


Subject(s)
Cartilage, Articular , Fibrin , Biocompatible Materials/chemistry , Cartilage, Articular/pathology , Tissue Engineering , Tissue Scaffolds/chemistry
8.
Cancers (Basel) ; 14(16)2022 Aug 16.
Article in English | MEDLINE | ID: mdl-36010940

ABSTRACT

Gastrointestinal adenocarcinomas are one of the world's deadliest cancers. Cancer stem cells and the tissue microenvironment are highly regulated by cell and molecular mechanisms. Cancer stem cells are essential for maintenance and progression and are associated with resistance to conventional treatments. This article reviews the current knowledge of the role of the microenvironment during the primary establishment of gastrointestinal adenocarcinomas in the stomach, colon, and rectum and its relationship with cancer stem cells. We also describe novel developments in cancer therapeutics, such as targeted therapy, and discuss the advantages and disadvantages of different treatments for improving gastrointestinal cancer prognosis.

9.
Life (Basel) ; 12(8)2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35892919

ABSTRACT

Cardiovascular diseases are a leading cause of death worldwide. Current treatments directed at heart repair have several disadvantages, such as a lack of donors for heart transplantation or non-bioactive inert materials for replacing damaged tissue. Because of the natural lack of regeneration of cardiomyocytes, new treatment strategies involve stimulating heart tissue regeneration. The basic three elements of cardiac tissue engineering (cells, growth factors, and scaffolds) are described in this review, with a highlight on the role of artificial scaffolds. Scaffolds for cardiac tissue engineering are tridimensional porous structures that imitate the extracellular heart matrix, with the ability to promote cell adhesion, migration, differentiation, and proliferation. In the heart, there is an important requirement to provide scaffold cellular attachment, but scaffolds also need to permit mechanical contractility and electrical conductivity. For researchers working in cardiac tissue engineering, there is an important need to choose an adequate artificial scaffold biofabrication technique, as well as the ideal biocompatible biodegradable biomaterial for scaffold construction. Finally, there are many suitable options for researchers to obtain scaffolds that promote cell-electrical interactions and tissue repair, reaching the goal of cardiac tissue engineering.

10.
Acta Chim Slov ; 69(1): 49-59, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35298022

ABSTRACT

An HPLC-UV/FLD method for simultaneous detection of ten antibiotics in surface waters was developed. Antibiotics were extracted from water using solid phase extraction. An Atlantis T3 column was used with acetonitrile and 0.05% trifluoroacetic acid as a mobile phase for separation, with a total running time of 45 min. Signal detection was performed at 280 nm; fluoroquinolones were additionally quantified by fluorescence detection. Validation parameters such as linearity, recovery and precision were evaluated. The limits of detection (LOD) in river waters were in the range 0.1-1.3 µg/L for antibiotics detected by UV, and 0.039 and 0.073 µg/Lfor fluoroquinolones detected by FLD. LOD are sufficiently low to consider this method as a first alternative for HPLC-MS methods that will allow alerting for the presence of antibiotics in surface waters. This screening method is rapid, sensitive, reproducible and economical.


Subject(s)
Anti-Bacterial Agents , Water Pollutants, Chemical , Chromatography, High Pressure Liquid/methods , Mass Spectrometry , Solid Phase Extraction/methods
11.
Front Public Health ; 9: 728690, 2021.
Article in English | MEDLINE | ID: mdl-34900890

ABSTRACT

Mexico has become one of the most highly affected countries by coronavirus disease 2019 (COVID-19) pandemic in Latin America. Therefore, efficient vaccination programs are needed to address COVID-19 pandemic. Although recent advances around the world have made it possible to develop vaccines in record time, there has been increasing fear and misinformation around the vaccines. Hence, understanding vaccine hesitancy is imperative for modeling successful vaccination strategies. In this study, we analyzed the attitude and perceptions toward COVID-19 vaccination, in a Mexican population (n = 1,512), using the proposed COVID-19 Vaccine Acceptance and Hesitancy Questionnaire (COV-AHQ) (Cronbach's alpha > 0.8), which evaluates a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parent toward vaccination of children; furthermore, a section including sociodemographic variables was included. According to the results of this study, the statistical correlation analysis of the general vaccination posture seems to correlate significantly (p < 0.05) with a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, hesitancy of parent toward vaccination of children, willingness to get COVID-19 vaccine, previous influenza vaccination, perception of the vaccine that could help the economy of country, occupation, gender, age, and participants actively researching COVID-19 vaccine information. An in-depth analysis assisted by binary logistic regression concluded that the young adult population around ages 18-34 years are the most likely to get vaccinated. This posture seems to be highly influenced by a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parents toward vaccination of children. While their own personal religious beliefs and economic status, the level of education does not seem to have an effect on the willingness to get vaccinated neither did having a previous COVID-19 diagnosis or even knowing someone with a positive COVID-19 diagnosis. Health authorities and policymakers could use the results of this study to aid in modeling vaccination programs and strategies and identify population groups with high vaccine hesitancy prevalence and assess significant public health issues.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , COVID-19 Testing , Child , Cross-Sectional Studies , Humans , Mexico/epidemiology , Pandemics , SARS-CoV-2 , Surveys and Questionnaires , Vaccination Hesitancy , Young Adult
12.
Life (Basel) ; 11(11)2021 Nov 05.
Article in English | MEDLINE | ID: mdl-34833063

ABSTRACT

Pancreatic cancer is the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve the non-specific use of chemotherapeutical agents such as 5-FU, capecitabine, gemcitabine, paclitaxel, cisplatin, oxaliplatin, or irinotecan, which produce several side effects. This review focuses on the use of targeted nanoparticles, such as metallic nanoparticles, polymeric nanoparticles, liposomes, micelles, and carbon nanotubes as an alternative to standard treatment for pancreatic cancer. The principal objective of nanoparticles is reduction of the side effects that conventional treatments produce, mostly because of their non-specificity. Several molecular markers of pancreatic cancer cells have been studied to target nanoparticles and improve current treatment. Therefore, properly functionalized nanoparticles with specific aptamers or antibodies can be used to recognize pancreatic cancer cells. Once cancer is recognized, these nanoparticles can attack the tumor by drug delivery, gene therapy, or hyperthermia.

13.
Pharmaceutics ; 13(7)2021 Jul 10.
Article in English | MEDLINE | ID: mdl-34371753

ABSTRACT

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. TRAIL has been widely studied as a novel strategy for tumor elimination, as cancer cells overexpress TRAIL death receptors, inducing apoptosis and inhibiting blood vessel formation. However, cancer stem cells (CSCs), which are the main culprits responsible for therapy resistance and cancer remission, can easily develop evasion mechanisms for TRAIL apoptosis. By further modifying their properties, they take advantage of this molecule to improve survival and angiogenesis. The molecular mechanisms that CSCs use for TRAIL resistance and angiogenesis development are not well elucidated. Recent research has shown that proteins and transcription factors from the cell cycle, survival, and invasion pathways are involved. This review summarizes the main mechanism of cell adaption by TRAIL to promote response angiogenic or pro-angiogenic intermediates that facilitate TRAIL resistance regulation and cancer progression by CSCs and novel strategies to induce apoptosis.

14.
World J Gastroenterol ; 27(26): 4160-4171, 2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34326616

ABSTRACT

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that causes coronavirus disease-2019 (COVID-19) has provoked a global pandemic, mainly affecting the respiratory tract; however, a percentage of infected individuals can develop gastrointestinal (GI) symptoms. Some studies describe the development of GI symptoms and how they affect the progression of COVID-19. In this review, we summarize the main mechanisms associated with gut damage during infection by SARS-CoV-2 as well as other organs such as the liver and pancreas. Not only are host factors associated with severe COVID-19 but intestinal microbiota dysbiosis is also observed in patients with severe disease.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Gastrointestinal Microbiome , COVID-19/complications , Dysbiosis , Gastrointestinal Diseases/virology , Gastrointestinal Tract , Humans , Inflammation/virology
15.
Front Public Health ; 9: 669057, 2021.
Article in English | MEDLINE | ID: mdl-34041219

ABSTRACT

To mitigate the COVID-19 infection, many world governments endorsed the cessation of non-essential activities, such as the school attendance, forcing a shift of the teaching model to the virtual classroom. From this shift, several changes in the teaching paradigm derived, in addition to the COVID-19 pandemic, which could have an impact in academic professional's mental health. In the present work we show the application of a modified version of the adapted COVID-19 stress scales (ACSS) which also included teaching anxiety and preparedness, and resilience for academic professionals in Mexico. These scales were applied during the unprecedented transformation of the education system undergone in the COVID-19 quarantine. Most of the studied variables: gender, age, academic degree, household occupants, having a disease, teaching level, teaching mode, work hours, resilience, teaching anxiety and preparedness, and fear of being an asymptomatic patient (FOBAP), showed significant statistical correlation between each other (p < 0.050) and to the 6 areas of the ACSS (danger, contamination, social economical, xenophobia, traumatic stress, and compulsive checking). Our results further showed that the perceived stress and anxiety fell into the category of Absent to Mild, with only the danger section of the ACSS falling into the Moderate category. Finally, the resilience generated throughout the quarantine was very high, which seems to be a predictor of adaptation the academic professional has undergone to cope with stress.


Subject(s)
COVID-19 , Mental Health , Pandemics , Resilience, Psychological , Anxiety/epidemiology , Humans , Mexico/epidemiology , SARS-CoV-2 , School Teachers , Stress, Psychological
16.
Data Brief ; 34: 106733, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33521178

ABSTRACT

The dataset presented examines the levels of stress persisting in healthcare professionals of the Northeast region of Mexico. Using an online platform to obtain data, a survey was developed and distributed through electronic means during a 6-week period covering July and August 2020, considered one of the periods with the highest reported COVID cases in Mexico. Our survey looked at six major stress developing areas: danger, fear of contamination, social economic consequences, xenophobia, compulsive checking and reassurance seeking, and traumatic stress; we added an extra question to assess fear of being an asymptomatic patient. The data was statistically analyzed looking for correlations and dependencies. Thus, helping in policy and decision-making processes to assist and manage stress in healthcare professionals.

17.
Article in English | MEDLINE | ID: mdl-35010556

ABSTRACT

COVID-19 vaccination programs continue in child populations. Thus, parents' attitude towards COVID-19 vaccination of their children is crucial for these strategies to succeed. The present study derives from the application of an online COVID-19 Vaccine Acceptance & Hesitancy Questionnaire (COV-AHQ) in which we measure parent's hesitancy towards children's vaccination (section 4 of the COV-AHQ) and other significant factors. A logistic regression analysis with backward stepwise method was used to quantify the associations between factors and parent's hesitancy. According to the correlation analysis, the most representative factors predicting vaccine hesitancy/acceptance were positive attitude towards vaccination, parents believing that the COVID-19 vaccine will enhance the economic situation of the country, parents actively researching information, having the willingness to obtain the COVID-19 vaccine themselves, and the possibility of their children developing adverse effects. Our findings also showed that parents are highly interested in having their children vaccinated. Nonetheless, parents expressed high levels of concern involving their children in developing adverse effects from the vaccine. In addition, obtaining influenza immunization prompted interest in obtaining the COVID-19 vaccine, and younger-aged parents are much more concerned with having their children vaccinated. Therefore, in order to ensure successful vaccination programs, policymakers and health authorities should design strategies to gain confidence and provide security amongst the population, including giving continuous information about the benefits of vaccination and presenting the frequency of side effects to bring parents on board with vaccinating their children.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Child , Cross-Sectional Studies , Humans , Mexico , SARS-CoV-2 , Vaccination , Vaccination Hesitancy
18.
Article in English | MEDLINE | ID: mdl-33086744

ABSTRACT

The world is currently subjected to the worst health crisis documented in modern history: an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID-19 adds even more so to healthcare professionals in particular, depending on their area, specialty, and type of work. Here we investigated what are the tendencies or areas most affected. Through an adaptation of the original COVID-stress scales, we developed a remote, fast test designed for healthcare professionals in the northeastern part of Mexico, an important part of the country with economic and cultural ties to the United States. Our results showed four key correlations as highly dependent: work area-xenophobia (p < 0.045), work with COVID patients-traumatic stress (p < 0.001), total number of COVID patients per day-traumatic stress (p < 0.027), and total number of COVID patients-compulsive checking and reassurance. Overall, we concluded that normal levels of stress have increased (mild-moderate). Additionally, we determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.


Subject(s)
Coronavirus Infections/epidemiology , Health Personnel/psychology , Occupational Stress/epidemiology , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Coronavirus Infections/psychology , Humans , Mexico/epidemiology , Pandemics , Pneumonia, Viral/psychology , Prevalence , SARS-CoV-2 , Surveys and Questionnaires
19.
Cardiovasc Eng Technol ; 11(2): 205-218, 2020 04.
Article in English | MEDLINE | ID: mdl-31916039

ABSTRACT

PURPOSE: The objective of this study was to bioengineer 3D patches from cardiac myocytes that have been reprogrammed from human adipogenic mesenchymal stem cells (hADMSCs). METHODS: Human adipogenic mesenchymal stem cells (hADMSCs) were reprogrammed to form cardiac myocytes using transcription factors ETS2 and MESP1. Reprogrammed cardiac myocytes were cultured in a fibrin gel to bioengineer 3D patch patches. The effect of initial plating density (1-25 million cells per patch), time (28-day culture period) and treatment with 1 µM isoproterenol and 1 µM epinephrine were evaluated. RESULTS: 3D patches were fabricated using cardiac myocytes that have been reprogrammed from hADMSCs. Based on optimization studies, it was determined that 10 million cells were needed to bioengineer a single patch, that measured 2 × 2 cm2. Furthermore, 3D patches fabricated 10 million cells were stable in culture for up to 28 days. Treatment of 3D patches with 1 µM isoproterenol and 1 µM epinephrine resulted in an increase in the electrical properties, as measured by electrical impulse amplitude and frequency. An increase in the expression of mTOR, KCNV1, GJA5, KCNJ16, CTNNT2, KCNV2, MYO3, FOXO1 and KCND2 was noted in response to treatment of 3D patches with isoproterenol and epinephrine. CONCLUSION: Based on the results of this study, there is evidence to support the successful fabrication of a highly functional 3D patches with measurable electrical activity using cardiac myocytes reprogrammed from hADMSCs. 3D patches fabricated using optimal conductions described in this study can be used to improve the functional properties of failing hearts. Predominantly, in case of the infarcted hearts with partial loss of electrical activity, the electrical properties of the 3D patches may restore the electrical activity of the heart.


Subject(s)
Adipogenesis , Cellular Reprogramming Techniques , Cellular Reprogramming , Heart Failure/surgery , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Myocytes, Cardiac/transplantation , Tissue Engineering , Adrenergic Agonists/pharmacology , Cells, Cultured , Electric Conductivity , Epinephrine/pharmacology , Fibrin/metabolism , Gene Expression Regulation , Heart Failure/genetics , Heart Failure/metabolism , Heart Failure/physiopathology , Humans , Isoproterenol/pharmacology , Membrane Potentials , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Time Factors
20.
J Tissue Eng Regen Med ; 14(2): 306-318, 2020 02.
Article in English | MEDLINE | ID: mdl-31821703

ABSTRACT

Clinical trials using human adipogenic mesenchymal stem cells (hAdMSCs) for the treatment of cardiac diseases have shown improvement in cardiac function and were proven safe. However, hAdMSCs do not convert efficiently into cardiomyocytes (CMs) or vasculature. Thus, reprogramming hAdMSCs into myocyte progenitors may fare better in future investigations. To reprogramme hAdMSCs into electrically conductive cardiac progenitor cells, we pioneered a three-step reprogramming strategy that uses proven MESP1/ETS2 transcription factors, ß-adrenergic and hypoxic signalling induced in three-dimensional (3D) cardiospheres. In Stage 1, ETS2 and MESP1 activated NNKX2.5, TBX5, MEF2C, dHAND, and GATA4 during the conversion of hAdMSCs into cardiac progenitor cells. Next, in Stage 2, ß2AR activation repositioned cardiac progenitors into de novo immature conductive cardiac cells, along with the appearance of RYR2, CAV2.1, CAV3.1, NAV1.5, SERCA2, and CX45 gene transcripts and displayed action potentials. In Stage 3, electrical conduction that was fostered by 3D cardiospheres formed in a Synthecon®, Inc. rotating bioreactor induced the appearance of hypoxic genes: HIF-1α/ß, PCG 1α/ß, and NOS2, which coincided with the robust activation of adult contractile genes including MLC2v, TNNT2, and TNNI3, ion channel genes, and the appearance of hyperpolarization-activated and cyclic nucleotide-gated channels (HCN1-4). Conduction velocities doubled to ~200 mm/s after hypoxia and doubled yet again after dissociation of the 3D cell clusters to ~400 mm/s. By comparison, normal conduction velocities within working ventricular myocytes in the whole heart range from 0.5 to 1 m/s. Epinephrine stimulation of stage 3 cardiac cells in patches resulted in an increase in amplitude of the electrical wave, indicative of conductive cardiac cells. Our efficient protocol that converted hAdMSCs into highly conductive cardiac progenitors demonstrated the potential utilization of stage 3 cells for tissue engineering applications for cardiac repair.


Subject(s)
Cell Culture Techniques/methods , Mesenchymal Stem Cells/cytology , Receptors, Adrenergic, beta/metabolism , Adipogenesis , Adrenergic Agents , Bioreactors , Cell Differentiation/physiology , Cell Proliferation , Electric Conductivity , Epinephrine/pharmacology , Humans , Hypoxia , Kinetics , Myocytes, Cardiac/cytology , Signal Transduction , Tissue Engineering/instrumentation , Tissue Engineering/methods , Tissue Scaffolds , Transcription Factors/metabolism
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