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Topic Review
Endothelial Cells in Schizophrenia
Schizophrenia (SCZ) is an articulated psychiatric syndrome whose faded etiologic framework is characterized by a combination of genetic, epigenetic, and environmental factors. It is notoriously explained by an intertwining of a positive and negative symptomatology, from Crow’s SCZ classification in type I (with a syndromic picture marked by a positive clinical condition) and type II (with a negative evolution of the clinical conditions), and subsequent debate, until the last Diagnostic Statistic Manual classification.
  • 567
  • 01 Feb 2024
Topic Review
Microbiome on Immunotherapy for Gastroesophageal Cancer
Esophageal cancer (EC) is a highly aggressive malignancy, comprising two main subtypes, esophageal squamous-cell carcinoma/ESCC and esophageal adenocarcinoma/EAC. Gastric cancer (GC) has been identified as a disease caused by a combination of genetic, molecular, and environmental factors, with H. pylori infection being the most common factor among them.
  • 559
  • 20 Oct 2023
Topic Review
Sexual Dimorphisms in Endothelial Cell Functions in PAD
Peripheral artery disease (PAD) is caused by blocked arteries due to atherosclerosis and/or thrombosis which reduce blood flow to the lower limbs. It results in major morbidity, including ischemic limb, claudication, and amputation, with patients also suffering a heightened risk of heart attack, stroke, and death.
  • 548
  • 24 Jan 2024
Topic Review
Venous Minus Arterial Carbon Dioxide Gradients in Monitoring
According to Fick’s principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the venous concentration of the substance. Therefore, the mixed or central venous minus arterial CO2 content difference depends on cardiac output (CO). Assuming a linear relationship between CO2 content and partial pressure, central or mixed venous minus arterial PCO2 differences (Pcv-aCO2 and Pmv-aCO2) are directly related to CO. Nevertheless, this relationship is affected by alterations in the CO2Hb dissociation curve induced by metabolic acidosis, hemodilution, the Haldane effect, and changes in CO2 production (VCO2). In addition, Pcv-aCO2 and Pmv-aCO2 are not interchangeable. Despite these confounders, CO is a main determinant of Pcv-aCO2. Since in a study performed in septic shock patients, Pmv-aCO2 was correlated with changes in sublingual microcirculation but not with those in CO, it has been proposed as a monitor for microcirculation. The respiratory quotient (RQ)—RQ = VCO2/O2 consumption—sharply increases in anaerobic situations induced by exercise or critical reductions in O2 transport. This results from anaerobic VCO2 secondary to bicarbonate buffering of anaerobically generated protons. The measurement of RQ requires expired gas analysis by a metabolic cart, which is not usually available. Thus, some studies have suggested that the ratio of Pcv-aCO2 to arterial minus central venous O2 content (Pcv-aCO2/Ca-cvO2) might be a surrogate for RQ and tissue oxygenation. 
  • 542
  • 14 Jul 2023
Topic Review
Post Heart Attack DNA Methylation: A Pilot Study
Myocardial infarction (MI) induces systemic biological changes, some of which may be reflected in DNA methylation patterns. This study investigates whether MI survivors retain distinct epigenetic signatures detectable in saliva DNA, a convenient and non-invasive biological sample. In a retrospective case-control design, genome-wide DNA methylation was assessed using the Illumina EPIC 850K array in saliva samples from 329 MI survivors and 1,438 age-matched healthy controls. After stringent quality control and removal of sex chromosome probes, methylation β-values at autosomal CpG sites were compared using the Mann–Whitney U test. Differentially methylated positions (DMPs) were defined using a significance threshold of p < 2×10⁻⁴ (FDR q < 0.05). Forty CpG sites showed significant methylation differences between MI survivors and controls. The majority (34/40) were hypermethylated in the MI group. Notable DMPs included loci in SELP, IRX5, AVPR1A, KCNH2, and CHGA, suggesting involvement of inflammatory, cardiac conduction, and neurohormonal pathways. Several genes had multiple significant CpGs, reinforcing their potential relevance. The largest effect was observed at ICAM5 (β ~3.9%). This study identifies a reproducible set of differentially methylated loci in saliva DNA of MI survivors, persisting up to three years post-event. These epigenetic changes may reflect both lasting physiological responses to MI and potential pre-existing risk markers. The findings support saliva-based methylation profiling as a viable tool for exploring cardiovascular epigenetics and highlight novel candidate genes for further investigation.
  • 541
  • 11 Jul 2025
Topic Review
Traumatic Brain Injury Recovery with Photobiomodulation
Traumatic brain injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributable to TBI's heterogenous and complex pathophysiology. Photobiomodulation (PBM), which employs specific red to near infrared light wavelengths to modulate brain functions, may be a promising therapy to address TBI's complex pathophysiology in a single intervention. PBM's potential for success could be further fulfilled by optimizing the parameters such as pulse frequencies. 
  • 531
  • 28 Feb 2024
Topic Review
Regenerating Myofibers after an Acute Muscle Injury
Injury to skeletal muscle through trauma, physical activity, or disease initiates a process called muscle regeneration. When injured myofibers undergo necrosis, muscle regeneration gives rise to myofibers that have myonuclei in a central position, which contrasts the normal, peripheral position of myonuclei. Myofibers with central myonuclei are called regenerating myofibers and are the hallmark feature of muscle regeneration. An important and underappreciated aspect of muscle regeneration is the maturation of regenerating myofibers into a normal sized myofiber with peripheral myonuclei. Strikingly, very little is known about processes that govern regenerating myofiber maturation after muscle injury. 
  • 519
  • 19 Oct 2023
Topic Review
Novel Biomarkers of Bone Metabolism
Bone represents a metabolically active tissue subject to continuous remodeling orchestrated by the dynamic interplay between osteoblasts and osteoclasts. These cellular processes are modulated by a complex interplay of biochemical and mechanical factors, which are instrumental in assessing bone remodeling. This comprehensive evaluation aids in detecting disorders arising from imbalances between bone formation and reabsorption. Osteoporosis, characterized by a reduction in bone mass and strength leading to heightened bone fragility and susceptibility to fractures, is one of the more prevalent chronic diseases. Some epidemiological studies, especially in patients with chronic kidney disease (CKD), have identified an association between osteoporosis and vascular calcification. Notably, low bone mineral density has been linked to an increased incidence of aortic calcification, with shared molecules, mechanisms, and pathways between the two processes. Certain molecules emerging from these shared pathways can serve as biomarkers for bone and mineral metabolism. Detecting and evaluating these alterations early is crucial, requiring the identification of biomarkers that are reliable for early intervention. While traditional biomarkers for bone remodeling and vascular calcification exist, they suffer from limitations such as low specificity, low sensitivity, and conflicting results across studies. In response, efforts are underway to explore new, more specific biomarkers that can detect alterations at earlier stages. 
  • 504
  • 05 Mar 2024
Topic Review
Non-Enzymatic Modification of Aminophospholipids by Carbonyl-Amine Reactions
Non-enzymatic modification of aminophospholipids by lipid peroxidation-derived aldehydes and reducing sugars through carbonyl-amine reactions are thought to contribute to the age-related deterioration of cellular membranes and to the pathogenesis of diabetic complications. Much evidence demonstrates the modification of aminophospholipids by glycation, glycoxidation and lipoxidation reactions. Therefore, a number of early and advanced Maillard reaction-lipid products have been detected and quantified in different biological membranes. These modifications may be accumulated during aging and diabetes, introducing changes in cell membrane physico-chemical and biological properties.
  • 503
  • 15 Nov 2023
Topic Review
Pathophysiology of High Altitude Illnesses
High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms effect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs.
  • 499
  • 16 May 2023
Topic Review
Role of Sensory Nerves in Pulmonary Fibrosis
Pulmonary fibrosis (PF) is a disease in which the lungs become scarred over time. It can result from occupational exposure, genetic defects, acute lung injury, or idiopathic causes. Sensory nerves are responsible for detecting harmful airborne stimuli and provide input to a variety of cells within the lungs, including airways and blood vessels. They play a critical role in regulating cardiopulmonary functions and maintaining homeostasis in healthy lungs. This review discusses the various effects of sensory nerve signaling in the setting of pulmonary fibrosis.
  • 450
  • 01 Apr 2024
Topic Review
Signaling Pathways in Hypothalamic Neurons with Aging
The hypothalamus is an important regulator of autonomic and endocrine functions also involved in aging regulation. The aging process in the hypothalamus is accompanied by disturbed intracellular signaling including insulin/insulin-like growth factor-1 (IGF-1)/growth hormone (GH), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/the mammalian target of rapamycin (mTOR), mitogen activated protein kinase (MAPK), janus kinase (JAK)/signal transducer and activator of transcription (STAT), AMP-activated protein kinase (AMPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), and nitric oxide (NO). 
  • 429
  • 18 Oct 2023
Topic Review
Extracellular Vesicle-Mediated Metabolic Reprogramming and TME Remodeling inMetastasis
It is increasingly recognized that the complex heterogeneous nature of the tumor microenvironment plays a critical role in the evolution and progression of cancer. The communication between matrix cells within the tumor microenvironment (TME), via extracellular vesicles, serves as an essential mediator for the development, recurrence, and metastatic dissemination of several cancer types. The role of extracellular vesicles (EVs) within the tumor microenvironment appears to be multifaceted and bidirectional as the initial release of EVs from cancer cells leads to the recruitment and activation of stromal cells, which includes cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAM), cancer-associated endothelial cells (CAEC), and mesenchymal stem cells (MSC). As tumor growth progresses, evidence suggests that EVs released from surrounding stromal cells drive the epithelial-to-mesenchymal transition (EMT) of cancer cells, and thus their progression to more metastatic phenotypes. Complementarily, as the release of EVs is enhanced during tumor growth, for certain tumors it allows their widespread diffusion and provides them with the potential to establish the pre-metastatic niche, which is necessary for the successful dissemination, colonization, and expansion of these cells to distant organ sites.
  • 428
  • 27 Sep 2023
Topic Review
SPINA Carb
SPINA Carb is a physiological approach for the quantitative evaluation of insulin-glucose homeostasis. It delivers calculated biomarkers for pancreatic beta-cell function (SPINA-GBeta) and insulin sensitivity (SPINA-GR), and a static disposition index (SPINA-DI) as an estimate for the loop gain of the feedback loop.
  • 336
  • 20 Oct 2025
Topic Review
Stress Is Associated with Lowered DNA Methylation
Chronic psychological stress is known to have physiological impacts and may involve epigenetic modifications. We investigated whether individuals with consistently high self-reported stress levels exhibit differential DNA methylation at specific CpG sites that have been associated with fibromyalgia, a chronic pain syndrome. Saliva DNA from two cohorts – a high-stress group (N = 357, 63% male, mean age 42 ± 1.8) and a low-stress comparison group (N = 37, 58% male, mean age 41 ± 2.0) – was analyzed using an Illumina Infinium methylation microarray (EPIC v2 “Mercury” beadchip) covering >850,000 CpG sites. We focused on three specific CpG loci (cg15957394, cg13348458, cg25294185) previously identified as significantly hypomethylated in fibromyalgia patients compared to healthy controls. The average methylation across these sites (a composite “Epi Vitality” Muhdo Health index) was compared between groups. The high-stress cohort showed a significantly lower mean methylation (mean β = 0.248) than the low-stress group (mean β = 0.271, Mann–Whitney U test p = 0.0225). Median methylation in the high-stress group was 0.233 (interquartile range, IQR, 0.195–0.291) vs. 0.280 (IQR 0.217–0.310) in low-stress subjects. This indicates that chronic high stress is associated with a subtle but significant DNA hypomethylation signature in saliva, similar in direction to that observed in fibromyalgia. Our findings provide preliminary evidence linking psychological stress with specific epigenetic changes that have been implicated in chronic pain, supporting the hypothesis that chronic stress and fibromyalgia may share common epigenetic pathways.
  • 208
  • 22 Jul 2025
Topic Review
The Walla Emotion Model
The Walla Emotion Model provides a distinct perspective on the often-interchangeable terms used in emotion research: affective processing, feelings, and emotions. The primary aim is to establish clearer, more neurobiologically grounded definitions to facilitate more precise research and understanding.
  • 143
  • 08 Aug 2025
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