Miguel Varoni, a well-known actor, director, and producer, has always prioritized his health, especially given his history as a former smoker. Despite stopping smoking 11 years ago, he remained aware of his elevated risk for lung cancer. Varoni admitted to being afraid of screening and lacking knowledge about the process, which led him to postpone it.
Overcoming Apprehension and Sharing His Story
Varoni's decision to undergo lung cancer screening came after overcoming his initial apprehension. He is now sharing his story as part of Merck's "Focus on Your Lungs" campaign, a collaborative effort with the GO2 Foundation, Lung Cancer Research Foundation, and Lung Cancer Foundation of America. The campaign aims to educate people about lung cancer risks and demystify the screening process. The website FocusOnYourLungs.com offers a short quiz to help individuals assess their eligibility for lung cancer screening.
The Role of Support: Catherine Siachoque's Encouragement
Varoni's wife, Catherine Siachoque, a renowned actress and Telenovela star, played a crucial role in helping him understand his risk for lung cancer and his eligibility for screening. She provided unwavering support, encouraging him to discuss his concerns with his doctor and schedule the necessary appointments. Siachoque was by his side throughout the entire process. She emphasized the importance of family as her driving force and joy, stating that when it became clear that Varoni was at high risk for lung cancer, they knew they had to take action.
The Screening Process: A Low-Dose CT Scan
After confirming his eligibility, Varoni's doctor ordered a low-dose CT (computed tomography) scan, also known as an LDCT. The scan involved Varoni lying on a table while an X-ray machine took pictures of his lungs. The procedure took less than 10 minutes and did not require medication or needles. Varoni described the screening as a much less daunting experience than he had imagined.
"Ladrón Que Roba a Ladrón": A Jaunty Heist Picture
Miguel Varoni also starred in the heist picture "Ladrón Que Roba a Ladrón" (A Thief Who Steals From a Thief), where he played Emilio, who teams up with Alejandro (Fernando Colunga) to fleece a corrupt TV infomercial guru. The film features a multiethnic ensemble cast and tells the story of working-class heroes who pose as "the help" at the mansion of the corrupt guru to steal his gold.
Read also: Understanding Fad Diets
Understanding Cholesterol: Separating Fact from Fiction
Cholesterol, a waxy, fat-like substance found in every cell of the human body, is essential for survival. It plays a key role in producing hormones, vitamin D, and bile acids, which help digest fats. There are two main types of cholesterol: low-density lipoprotein (LDL), often called “bad” cholesterol, and high-density lipoprotein (HDL), known as “good” cholesterol. LDL cholesterol can accumulate in the arteries, leading to plaque formation and increasing the risk of heart disease.
For decades, cholesterol has been blamed for heart disease and other health problems. However, modern research has shown that cholesterol is more complex than previously thought. Many misconceptions persist, leading to confusion about its true role in our health. One of the most widespread misconceptions is that cholesterol is entirely harmful and should be eliminated from the diet. In reality, cholesterol is vital for many bodily functions. Rather than focusing solely on cholesterol levels, experts now emphasize the importance of cholesterol balance and the role of inflammation in heart disease. While high LDL levels can contribute to plaque buildup, they are not the sole cause of heart problems.
For years, people were told to avoid cholesterol-rich foods like eggs, shrimp and dairy products to keep their cholesterol levels in check. However, scientific research has debunked this belief. The liver regulates cholesterol levels by adjusting its production based on dietary intake. A study published in the American Journal of Clinical Nutrition found that dietary cholesterol has little effect on blood cholesterol levels for most people. While high LDL cholesterol can be a risk factor for heart disease, it is not the only indicator of heart health. Many people with normal cholesterol levels still suffer from heart attacks and strokes. Research suggests that inflammation, insulin resistance, and oxidative stress are stronger predictors of heart disease than cholesterol alone. Factors such as diet, exercise, stress levels and genetics all contribute to cardiovascular health. Cholesterol is not the enemy it was once thought to be. It is a vital substance that the body needs to function properly. Instead, individuals should focus on maintaining a balanced diet rich in whole foods, exercising regularly, managing stress and avoiding processed foods and trans fats.
Childhood Obesity and Metabolic Syndrome: An Overview
The incidence of childhood obesity and metabolic syndrome has grown notably in recent years, becoming major public health burdens in developed countries. Nowadays, oxidative stress is well-recognized to be closely associated with the onset and progression of several obesity-related complications within the framework of a complex crosstalk involving other intertwined pathogenic events, such as inflammation, insulin disturbances, and dyslipidemia. Thus, understanding the molecular basis behind these oxidative dysregulations could provide new approaches for the diagnosis, prevention, and treatment of childhood obesity and associated disorders. In this respect, the transcriptomic characterization of miRNAs bares great potential because of their involvement in post-transcriptional modulation of genetic expression.
Childhood obesity is nowadays a pandemic health issue, affecting over 41 million children under five according to recent estimations from the World Health Organization. Obesity is closely related to various cardiovascular risk factors, such as hyperglycemia, dyslipidemia, and high blood pressure, which altogether constitute the so-called metabolic syndrome (MetS) and represent the main drivers of obesity-related deleterious repercussions over health. Notably, around one third of children with obesity suffer from MetS components, with insulin resistance (IR) being the most prevalent. Nevertheless, unlike the above-defined “metabolically unhealthy obesity” (MUO), part of the population with obesity does not present comorbidities, which is known as “metabolically healthy obesity” (MHO). Although obesity lacks a concrete etiology, it is known to be the consequence of a complex cluster of interrelated risk factors, including the microbiome, environmental, genetic, perinatal, nutritional, psychosocial, and metabolic factors. In particular, inflammation and oxidative stress (OS) have been described to be tightly interrelated in a vicious cycle that participates in many of the pathological processes behind obesity and related complications.
Read also: Weight Loss Guide Andalusia, AL
The Interplay of Inflammation and Oxidative Stress in Obesity
Fat accumulation triggers chronic inflammation through several molecular mechanisms, namely immune response activation, cytokine secretion, oxygen flow shrinkage, cellular necrosis, and disturbed lipid homeostasis. In this vein, increased cytokine secretion by adipocytes and subsequent subclinical inflammation is known to promote MetS in subjects with obesity. Cytokines also have a role in the synthesis of acute phase proteins and the invasion of innate immune cells into adipose tissue. Neutrophil infiltration has been proposed as the initial step in the recruitment of macrophages and other immune cells (such as T or B lymphocytes) within adipose tissue. These macrophages in adipose tissue are believed to originate from bone marrow monocytes. While obese fat has large quantities of the pro-inflammatory M1 type of macrophages, lean fat is concentrated in the M2 anti-inflammatory type of macrophages. Eosinophil levels, which are necessary for the maintenance of M2 macrophages, have been reported to be downregulated in obesity. Concurring with these data, hypereosinophilic mice have been found to be protected from IR, whereas mice lacking them develop more body fat, impaired glucose tolerance, and decreased insulin sensitivity. Finally, natural killer T cells can also play relevant roles in adipose tissue inflammation, thereby influencing the susceptibility to develop obesity and IR in a process in which natural killer T cells are influenced and influence the microbiome.
Within this proinflammatory environment, activated immune cells liberate reactive oxygen species (ROS) and, when sustained for prolonged time periods, provoke exacerbated OS. After binding their receptors, cytokines can both initiate ROS production and promote the induction of other inflammatory signals. Thus, proinflammatory cytokines such as interferon-𝛾 or IL6, and proinflammatory components such as lipopolysaccharide, have been found to increase nicotinamide adenine dinucleotide phosphate oxidase (NOX)-dependent ROS production. At the same time, the production of ROS may prime signaling cascades that bidirectionally promote proinflammatory gene expression. In this venue, reactive species can lead to inflammation through the activation of protein kinase C, c-Jun-N-terminal kinase, nuclear factor 𝜅B (NF-𝜅B), mitogen-activated protein kinases, or NOD-like receptor protein 3 inflammasome, among others. Along the process of repairing oxidatively damaged DNA, signaling cascades culminating in NF-𝜅B activation are triggered, leading to proinflammatory gene expression. Similarly, OS has been linked to monocyte adhesion to vascular endothelial cells, which also results in NF-𝜅B activation. In human macrophages, a marker of lipid oxidation, 8-isoprostane, is known to activate mitogen-activated protein kinases and lead to increased expression of inflammatory chemokines such as IL-8. Finally, OS mediates NOD-like receptor protein 3 inflammasome activation by means of the dissociation of the thioredoxin-interacting protein/thioredoxin (TRX) complex, thus allowing the interaction between thioredoxin-interacting protein and NOD-like receptor protein 3, and subsequently leading to its activation. Moreover, lipids, proteins, and nucleic acids can be modified under pro-oxidative environments, which may subsequently act as danger-associated molecular patterns (DAMPs) and provoke innate immune responses.
Accordingly, childhood obesity and MetS have repeatedly been associated with a sharpened pro-inflammatory milieu (i.e., increased cytokines, disturbed white blood cell counts) and impaired redox metabolism, this latter reflected in reduced content of endogenous and exogenous antioxidants and raised levels of oxidative damage byproducts. In this context, studies involving pediatric patients are of major interest to get new insights into the molecular basis behind the onset of obesity at early ages and, thus, to facilitate the development of efficient therapies to prevent further complications. To this end, it is critical to understand the contribution of genetic and epigenetic traits in childhood obesity and its comorbidities.
The Role of MicroRNAs (miRNAs) in Childhood Obesity
miRNAs are short (19-23 nucleotides), single-stranded, and non-coding RNA molecules participating in post-transcriptional regulation of genetic expression, which are known to modulate up to 60% of the genes encoded within the human genome. In particular, they act as regulators of messenger RNA (mRNA) degradation and as protein synthesis blockers by binding to untranslated regions (UTRs) of target mRNAs. Nevertheless, recent findings suggest that miRNAs might also up-regulate gene-transcription. As each miRNA is able to target above one hundred genes and, in turn, multiple miRNAs participate in the expression of the same transcript, miRNA dysregulations may provoke profound disturbances in a multitude of biological networks.
Although miRNAs modulate genetic expression within cells, they can also be loaded into extracellular vesicles (e.g., exosomes or microvesicles) and released to the circulation, thereby being protected against RNase degradation and allowing cell-to-cell communication. In this venue, miRNAs sorting into extracellular vesicles seems to be a selective process, although the mechanism by which the cells choose miRNAs to be loaded and secreted remains unclear. Interestingly, most body fluids (e.g., blood, breast milk, urine, or saliva) contain exosomes or microvesicles, opening the window to new transcriptomics strategies in biomedical research.
Read also: Beef jerky: A high-protein option for shedding pounds?
Many authors have previously delved into the potential role of miRNAs as predictors of obesity development in neonates and as biomarkers of early childhood obesity. In fact, childhood obesity has been described to be accompanied by profound deregulations in the circulating miRNA profile. On the one hand, it has been reported that obese mice adipocytes release more miRNA-containing exosomes compared to lean mice adipocytes. Besides these changes in absolute miRNA contents, obesity is also recognized to be the pathology with the highest percentage of genetic variants in the 3’UTR region of mRNAs, which modulate their interaction with miRNAs. Moreover, Mansego et al. proved that several miRNAs coding regions present CpG methylation patterns specific to childhood obesity, pinpointing to a role of epigenetic regulation in obesity development. For instance, higher Mediterranean diet adherence has been related to a switch toward healthier circulating miRNAs profile, whereas high-caloric diet consumption leads to increased levels of miRNAs involved in obesity development and progression. Furthermore, miRNAs are known to participate in appetite control in childhood obesity by regulating hormones such as leptin or neuropeptide Y. In this vein, growing evidence supports that miRNAs, diet, and gut microbiota may bidirectionally modulate each other. Thus, miRNA-10a-5p has been proposed to improve high fat diet (HFD)-triggered glucose intolerance and IR through the modulation of the microbiome and its metabolism.
External stimuli during fetal development also have great impact on the onset of obesity. Obesity induced by maternal diet negatively impacts offspring body composition in a process that is accompanied by age-dependent alterations in miRNA-582 expression. Joshi et al. reported that in utero exposure to maternal obesity provokes sexually dimorphic perturbations in miRNA profiles. Similarly, both paternal HFD and exercise have been described to elicit a sex-specific effect on T2DM risk in offspring by altering sperm miRNA expression. Finally, sex is also known to influence circulating concentrations of some miRNAs in adolescents with obesity, which in turn show sexually dimorphic associations with inflammatory biomarkers. This concurs with the general observation that female subjects are more susceptible to weight gain, although men are prone to suffer from obesity-related comorbidities. This could be mainly allocated to sex differences in adipose tissue distribution, as young men normally have higher visceral fat depots, whilst pre-menopausal women accumulate subcutaneous adipose tissue.
Numerous authors have also explored the plausible link between miRNAs and a myriad of childhood obesity-related comorbidities, such as MetS, T2DM, NAFLD, chronic kidney disease, nephropathy, endothelial dysfunction, colitis, or cancer. Interestingly, miRNAs have also shown potential as biomarkers of response to intervention strategies against obesity. In this respect, Liao et al. proved exercise-based strategies to affect some obesity-related miRNAs in childhood obesity. Also, liraglutide is known to promote the browning of white adipose tissue by downregulating miR-27b expression.
The Role of Adipogenesis, Insulin Metabolism, and Inflammation
Childhood obesity is a multifactorial disorder in which a number of closely interrelated pathogenic events participate, namely adipogenesis, insulin metabolism, inflammation, and OS. Since obesity can primarily be regarded as an abnormal or excessive fat accumulation, altered adipogenesis can be considered as a pivotal player in childhood obesity. In this vein, although most of the molecular pathways involved in adipogenesis are shared between subjects with and without obesity, the onset and progression of obesity have been related to specific miRNA perturbations along this process. Thus, patients with obesity showed a stronger downregulation of miRNAs involved in adipogenesis when compared to lean subjects. As expected, many of the miRNAs that are differentially expressed in visceral adipose tissue of children with obesity have been reported to be enriched in pathways related to lipid metabolism. Some of the most affected pathways at the transcriptomics level by these obesity-related miRNAs have been found to be fatty acid oxidation, ketogenesis, lipogenesis, and lipid uptake, which could be directly related to increased adipogenesis, fat mass gain, and liver steatosis.
Obesity and its common comorbidities are also characterized by profound disturbances in insulin homeostasis and related biological processes, such as carbohydrate and lipid metabolisms. Pancreatic β-cells are responsible for sensing glucose levels and mediate insulin secretion in a two-step process. First, glucose enters the β-cell, where it is metabolized in the glycolytic pathway and the tricarboxylic acid cycle to produce adenosine triphosphate (ATP). The increase in cellular ATP levels promotes the closure of ATP-sensitive potassium channels, provoking membrane depolarization and the opening of voltage-dependent calcium channels. The raise in cellular calcium content finally triggers insulin secretion. For the second phase, actin filaments need to be reorganized to accomplish the recruitment of intracellularly stored granules. Once released, insulin binds to the α chain of its membrane-located receptor, thus causing structural changes in the β chain thanks to tyrosine kinase mediated auto-phosphorylation of tyrosine residues. Then, phosphorylated receptors recruit intracellular components to initiate signaling pathways. Depending on the tissue and the intracellular substrate, insulin may promote glucose utilization and storage by activating glycolysis, glycogen synthesis, and adipogeneses; by inhibiting gluconeogenesis, lipolysis, and glucagon secretion; or by increasing glucose transport. Within this tangled crosstalk of intertwined processes, miRNAs are recognized to be directly involved in regulating insulin signaling and glucose metabolism at different levels, thereby being capable of promoting either insulin sensitivity or IR in subjects with obesity.
To conclude, a few authors have also described obesity-related miRNA dysregulations to be tightly correlated with a multitude of inflammation biomarkers, such as tumor necrosis factor α (TNFα), interleukin 1 receptor antagonist, IL-8, IL-15, procalcitonin, adiponectin, or C-reactive protein. In this vein, it has recently been demonstrated that the typical inflammatory status present in childhood obesity could modulate miRNA contents in adipocytes. Thus, the expression of miR-424 has been found to be higher in adipose tissue of children with obesity, whereas TNFα can bind to its promoter region and, consequently, decrease its transcription.
Gandhigram Trust: Empowering Rural Communities
Gandhigram Trust has been working tirelessly to enhance the socio-economic status of rural communities through interventions in healthcare, education, rehabilitation and community development.
Philosophy
The idea of Gandhigram was born to take forward the vision of empowering villages and enabling their holistic development. The organisation was the brainchild of Dr. TS. Soundaram and Dr. G. Ramachandran who were ardent followers of Gandhi and worked to incorporate his values in their work.
What They Do
- Education: Providing schooling to children in the communities they serve.
- Healthcare: Ensuring that no citizen is denied access to quality healthcare on account of their socio-economic status.
- Rehabilitation: Providing homes for sections of society that have been neglected and enabling them to reclaim the space that rightfully belongs to them.
- Community Development: Following Gandhian values to nurture self-employment through village industries and extension programs. Khadi is also an integral part of their mission.