Search Results (773)

This narrative case-based review describes the environmental and public health impacts in Chañaral, a town in northern Chile affected by the accumulation of copper mining tailings for the past 80 years. The review included 34 scientific articles published between 1978 and 2025. The keywords used were “mining tailings” and “Chañaral”, without year limits, and covering disciplines such as ecology, public health, environmental history, and territorial studies. The scientific evidence demonstrates the negative impacts on the ecosystem and the human population exposed to toxic metals and arsenic. Geomorphological and biogeochemical alterations have been found on the Chañaral coast, affecting marine biodiversity and water quality. In addition, epidemiological studies indicate exposure to toxic metals measured in street dust and urine, raising concerns on respiratory health in children and metabolic conditions in adults. According to the social sciences, the lack of environmental monitoring and human exposure data contributes to the high health risk perception in the population, posing the need to strengthen environmental monitoring, raise awareness on the risks of exposure to toxic metals, and promote mitigation and restoration strategies. These measures will contribute to sustainable conditions for the Chañaral community through the improvement of comprehensive public policies. Full article

Iron represents an essential element required for normal physiologic processes throughout organ systems. A vast network of transporters is involved not only in uptake of this element but in processing, oxidation, and recycling to maintain it in a tight balance to avoid excess storage. This complex network of transporters, including heme and ferroportin, among many others, are responsible for facilitating inter-organ tissue iron exchange and availability, contributing to overall heme homeostasis. However, exposure to high levels of iron can overwhelm compensatory mechanisms that result in its accumulation and toxicity. This is the case of patients with genetic diseases such as hemoglobinopathies who suffer from chronic anemia and require, in most instances, a lifetime of red blood cell transfusions to overcome disease crises. Thus, in light of the extensive role of iron in the body, the aim of this review is to present important metabolic pathways involved in iron homeostasis across the cardiovascular, reproductive, hematopoietic, urinary, respiratory, endocrine, and central nervous systems while contrasting these against negative effects caused by iron excess. Full article

Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, their short half-life requires frequent dosing and incurs high treatment costs. This study evaluates a novel peptide-based Anti-PCSK9 product aimed at providing sustained LDL-C reduction. Methods: A novel PCSK9 based-peptide conjugated to diphtheria toxoid (DT) was evaluated in various preclinical models: high-fat diet-fed C57BL/6 mice, APOB100/hCETP transgenic mice, BALB/c mice and normocholesterolemic non-human primates. Immunogenicity (Anti-PCSK9 antibody titers, binding affinity by SPR), pharmacodynamics (LDL-C levels, inhibition of PCSK9-LDLR interaction) and safety were assessed. Toxicity was evaluated in rodents, rabbits and dogs through clinical monitoring, histopathology, organ function and safety pharmacology studies. Results: The Anti-PCSK9 product induced robust and long-lasting immune response in all models antibody titers in BALB/c mice peaked by week 6 and persisted for 12 months. LDL-C reductions of 44% in APOB100/hCETP mice and 37% in C57BL/6 mice correlated with high antibody titers and strong PCSK9-binding affinities (85 and 49 RU), leading to 59% and 58% inhibition of PCSK9-LDLR interaction, respectively. Non-human primates showed sustained responses. No systemic toxicity was observed; injection-site reactions were mild and reversible. No adverse effects were detected on cardiovascular, neurological, or respiratory systems. Conclusions: This peptide-based Anti-PCSK9 therapy offers sustained efficacy and safety, representing a promising long-acting alternative for managing hypercholesterolemia. Full article

Amyotrophic lateral sclerosis (ALS) is still a heterogeneous neurodegenerative disorder that can be identified clinically and biologically, without a strong set of biomarkers that can adequately measure its fast rate of progression and molecular heterogeneity. In this review, we intend to consolidate the most relevant and timely advances in ALS biomarker discovery, in order to begin to bring molecular, imaging, genetic, and digital areas together for potential integration into a precision medicine approach to ALS. Our goal is to begin to display how several biomarkers in development (e.g., neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), TDP-43 aggregates, mitochondrial stress markers, inflammatory markers, etc.) are changing our understanding of ALS and ALS dynamics. We will attempt to provide a framework for thinking about biomarkers in a systematic way where our candidates are not signals alone but part of a tethered pathophysiological cascade. We are particularly interested in the fast progressor phenotype, a devastating and under-characterized subset of ALS due to a rapid axonal degeneration, early respiratory failure, and very short life span. We will try to highlight the salient molecular features of this ALS subtype, including SOD1 A5V toxicity, C9orf72 repeats, FUS variants, mitochondrial collapse, and impaired autophagy mechanisms, and relate these features to measurable blood and CSF (biomarkers) and imaging platforms. We will elaborate on several interesting tools, for example, single-cell transcriptomics, CSF exosomal cargo analysis, MRI techniques, and wearable sensor outputs that are developing into high-resolution windows of disease progression and onset. Instead of providing a static catalog, we plan on providing a conceptual roadmap to integrate biomarker panels that will allow for earlier diagnosis, real-time disease monitoring, and adaptive therapeutic trial design. We hope this synthesis will make a meaningful contribution to the shift from observational neurology to proactive biologically informed clinical care in ALS. Although there are still considerable obstacles to overcome, the intersection of a precise molecular or genetic association approach, digital phenotyping, and systems-level understandings may ultimately redefine how we monitor, care for, and treat this challenging neurodegenerative disease. Full article

Cardiovascular and metabolic disorders significantly reduce healthspan and lifespan, with oxidative stress being a major contributing factor. Oxidative stress, marked by elevated reactive oxygen species (ROS), disrupts cellular and systemic functions. One proposed mechanism involves TRPM2 (Transient Receptor Potential Melastatin2)-dependent Ca²⁺ dysregulation. These channels, activated by ROS (via ADP-ribose), not only respond to ROS but also amplify it, creating a self-sustaining cycle. Recent studies suggest that TRPM2 activation triggers a cascade of signals from intracellular organelles, enhancing ROS production and affecting cell physiology and viability. This review examines the role of TRPM2 channels in oxidative stress-associated cardiovascular and metabolic diseases. Oxidative stress induces TRPM2-mediated Ca²⁺ influx, leading to lysosomal damage and the release of Zn²⁺ from lysosomal stores to the mitochondria. In mitochondria, Zn²⁺ facilitates electron leakage from respiratory complexes, reducing membrane potential, increasing ROS production, and accelerating mitochondrial degradation. Excess ROS activates PARP1 in the nucleus, releasing ADP-ribose, a TRPM2 agonist, thus perpetuating the cycle. Lysosomes act as Ca²⁺-sensitive signalling platforms, delivering toxic Zn²⁺ signals to mitochondria. This represents a paradigm shift, proposing that the toxic effects of Ca²⁺ on mitochondria are not direct, but are instead mediated by lysosomes and subsequent Zn²⁺ release. This cycle exhibits a ‘domino’ effect, causing sequential and progressive decline in the function of lysosomes, mitochondria, and the nucleus—hallmarks of ageing and oxidative stress-related cardiovascular and metabolic diseases. These insights could lead to new therapeutic strategies for addressing the widespread issue of cardiovascular and metabolic diseases. Full article

Echium L. is a genus of flowering plants from the Boraginaceae family that includes several species traditionally used in herbal medicine. Echium spp. have been applied for treating wounds, urinary tract infections, inflammation, respiratory ailments, cardiovascular disorders, and microbial infections. The roots and flowers are most frequently used, typically prepared as decoctions or infusions. Phytochemical studies have identified diverse bioactive compounds, including phenolics, naphthoquinones, shikonins, fatty acids, sterols, terpenoids, amino acids, and toxic pyrrolizidine alkaloids. Reported pharmacological effects include antioxidant, antimicrobial, and cytotoxic activities, primarily attributed to polyphenolic and terpenoid content. However, the presence of toxic alkaloids also raises concerns regarding safety. This review provides a comprehensive overview of the ethnomedicinal uses, phytochemical components, and pharmacological activities of Echium species. The bioactivities observed in genus Echium L. substantiate the necessity for preclinical and clinical investigations to thoroughly elucidate and validate the therapeutic potential of this genus and emphasize its relevance in the development of novel therapeutic agents. Full article

COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin–angiotensin–aldosterone system (RAAS), the kininogen–kinin–kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects. Full article

Particulate matter (PM), a complex mixture of solid particles and liquid droplets, originates from both natural sources, such as sand, pollen, and marine salts, and anthropogenic activities, including vehicle emissions and industrial processes. While PM itself is not inherently toxic in all its forms, it often acts as a carrier of xenobiotic toxicants, such as heavy metals and organic pollutants, which adhere to its surface. This combination can result in synergistic toxic effects, significantly enhancing the potential harm to biological systems. Due to its small size and composition, PM can penetrate deep into the respiratory tract, acting as a physical “shuttle” that facilitates the distribution and bioavailability of toxic substances to distant organs. The omnipresence of PM in the environment leads to unavoidable and constant exposure, contributing to increased morbidity and mortality rates, particularly among vulnerable populations like the elderly, children, and individuals with pre-existing health conditions. This exposure also imposes a substantial financial burden on healthcare systems, as treating PM-related illnesses requires significant medical resources and leads to higher healthcare costs. Addressing these challenges necessitates effective mitigation strategies, including reducing PM exposure, improving air quality, and exploring novel approaches such as AI-based exposure prediction and nutritional interventions to protect public health and minimize the adverse effects of PM pollution. Full article

Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal ligation and puncture (CLP) was conducted in young adult (12–18 weeks) and aged (19–21 months) male C57BL/6 mice. Cardiac function was detected 20 h post-CLP. Additionally, cardiomyocytes isolated from young adult and aged male mice were used for assessments of mitochondrial respiratory function +/– TNFα or LPS. Protein levels of oxidative phosphorylation (OXPHOS), NADPH oxidase (NOX)2, NOX4, phosphor-STAT3 and STAT3 were determined in mouse hearts 24 h post-CLP and in cardiomyocytes following inflammatory stimuli. CLP significantly reduced cardiac contractility in both young and aged mice, with a higher incidence and greater severity of cardiac functional depression in the older group. Mitochondrial respiratory capacity was decreased in cardiomyocytes derived from aged mice, with increased susceptible to inflammatory toxic effects compared to those from young adult mice. The age-dependent changes were observed in myocardial OXPHOS complexes and NOX4. Importantly, CLP led to a significant increase in OXPHOS protein levels in the hearts of older mice, suggesting a possible compensatory response to decreased mitochondrial metabolic function and a greater potential for reactive oxygen species (ROS) generation. Our findings highlight that the response of aging-impaired mitochondria to inflammation may underlie the worsened cardiac functional depression in the aged group during sepsis. Full article

Internal combustion engine vehicles damage the environment and public health by emitting toxic fumes, such as CO₂ or CO and other trace compounds. The use of electric cars helps to reduce the emission of pollutants into the environment due to the use of batteries with no direct and local emissions. However, accidents of battery electric vehicles pose new challenges, such as thermal runaway. Such accidents can be serious and, in some cases, may result in uncontrolled overheating that causes the battery pack to spontaneously ignite. In particular, the most dangerous vehicles are heavy goods vehicles (HGVs), as they release a large amount of energy that generate high temperatures, poor visibility, and respiratory damage. This study aims to determine the potential consequences of large BEV fires in road tunnels using computational fluid dynamics (CFD). Furthermore, a comparison between a BEV and an ICEV fire shows the differences related to the thermal and the toxic impact. Furthermore, the adoption of a longitudinal ventilation system in the tunnel helped to mitigate the BEV fire risk, keeping a safer environment for tunnel users and rescue services through adequate smoke control. Full article

Volatile organic compounds (VOCs) are highly volatile chemicals in natural and anthropogenic environments, significantly affecting indoor air quality. Major sources of indoor VOCs include emissions from building materials, furnishings, and consumer products. Natural wood products release VOCs, including terpenes and aldehydes, which exert diverse health effects ranging from mild respiratory irritation to severe outcomes, such as formaldehyde-induced carcinogenicity. The temporal dynamics of VOC emissions were investigated, and the toxicological and physiological effects of the VOCs emitted by two types of natural wood, Korean Red Pine (Pinus densiflora) and Japanese Cypress (Chamaecyparis obtusa), were evaluated. Using female C57BL/6 mice as an animal model, the exposure setups included phytoncides, formaldehyde, and intact wood samples over short- and long-term durations. The exposure effects were assessed using oxidative stress markers, antioxidant enzyme activity, hepatic and renal biomarkers, and inflammatory cytokine profiles. Long-term exposure to Korean Red Pine and Japanese Cypress wood VOCs did not induce significant pathological changes. Japanese Cypress exhibited more distinct benefits, including enhanced oxidative stress mitigation, reduced systemic toxicity, and lower pro-inflammatory cytokine levels compared to the negative control group, attributable to its more favorable VOC emission profile. These findings highlight the potential health and environmental benefits of natural wood VOCs and offer valuable insights for optimizing timber use, improving indoor air quality, and informing public health policies. Full article

Military personnel deployed to Iraq and Afghanistan were exposed to emissions from open-air burn pits, where plastics, metals, and medical waste were incinerated. These exposures have been linked to deployment-related respiratory diseases (DRRD) and may also impact neurological health via the lung–brain axis. To investigate molecular mechanisms, adult male rats were exposed to filtered air, naphthalene (a representative volatile organic compound), or a combination of naphthalene and carbon black (surrogate for particulate matter; CBN) via whole-body inhalation (six hours/day, three consecutive days). Lung, brain, and plasma samples were collected 24 h after the final exposure. Pro-inflammatory biomarkers were assessed using multiplex electrochemiluminescence and western blot. Differentially expressed genes (DEGs) were identified by RNA sequencing, and elastic net modeling was used to define exposure-predictive gene signatures. CBN exposure altered inflammatory biomarkers across tissues, with activation of nuclear factor kappa B (NF-κB) signaling. In the lung, gene set enrichment revealed activated pathways related to proliferation and inflammation, while epithelial–mesenchymal transition (EMT) and oxidative phosphorylation were suppressed. In the brain, EMT, inflammation, and senescence pathways were activated, while ribosomal function and oxidative metabolism were downregulated. Elastic net modeling identified a lung gene signature predictive of CBN exposure, including Kcnq3, Tgfbr1, and Tm4sf19. These findings demonstrate that inhalation of a surrogate burn pit mixture induces inflammatory and metabolic gene expression changes in both lung and brain tissues, supporting the utility of this animal model for understanding systemic effects of airborne military toxicants and for identifying potential biomarkers relevant to DRRD and Veteran health. Full article

Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial condition associated with significant systemic complications such as cardiovascular disease (CVD), metabolic disorders, muscle wasting, and sarcopenia. While Body Mass Index (BMI) is a well-established indicator of obesity and has prognostic value in COPD, its role in predicting disease outcomes is complex. Muscle wasting is prevalent in COPD patients and exacerbates disease severity, contributing to poor physical performance, reduced quality of life, and increased mortality. Additionally, COPD is linked to metabolic disorders, such as dyslipidemia and diabetes, which contribute to systemic inflammation and worse prognosis and, therefore, should be treated. The systemic inflammatory response plays a central role in the development of sarcopenia. In this review, we highlight the mixed efficacy of statins in managing dyslipidemia in COPD, considering side effects, including muscle toxicity in such a frail population. Alternative lipid-lowering therapies and nutraceuticals, in addition to standard treatment, have the potential to target hypercholesterolemia, which is a coexisting condition present in more than 50% of all COPD patients, without worsening muscle wasting. The interference between adipose tissue and lung, and particularly the potential protective role of adiponectin, an adipocytokine with anti-inflammatory properties, is also reviewed. Respiratory, metabolic and muscular health in COPD is comprehensively assessed. Identifying and managing dyslipidemia and paying attention to other relevant COPD comorbidities, such as sarcopenia and muscle wasting, is important to improve the quality of life and to reduce the clinical burden of COPD patients. Future research should focus on understanding the relationships between these intimate mechanisms to facilitate specific treatment for systemic involvement of COPD. Full article

Vitexin and isovitexin are dietary flavonoids widely distributed in food and medicinal plants. They have attracted increasing attention owing to their diverse pharmacological activities and favorable safety profiles. These compounds exhibit therapeutic potential across multiple biological systems, including the immune, nervous, respiratory, cardiovascular, and endocrine systems, through antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective mechanisms. Although previous reviews have addressed the pharmacological effects of vitexin and isovitexin, most are limited in scope—either focusing solely on vitexin or restricted to specific disease models such as cancer or diabetes. Moreover, some studies are outdated and do not reflect the recent advances in synthetic modification, green extraction technologies, and systems pharmacology. This review aims to provide a comprehensive evaluation of the pharmacological properties, pharmacokinetics, and clinical relevance of vitexin and isovitexin, highlighting their potential in disease prevention and treatment. A literature search was conducted using Web of Science, PubMed, and Google Scholar, with keywords including “vitexin”, “isovitexin”, “disease”, and “mechanism”. Here, we summarize the current research on the pharmacological effects of vitexin and isovitexin in metabolic disorders, inflammatory diseases, cancer, and neurodegenerative conditions, focusing on their molecular mechanisms and therapeutic targets. Furthermore, we discussed their toxicity, bioavailability, pharmacokinetics, and clinical research findings. Vitexin and isovitexin hold promise as therapeutic agents or adjuncts for multiple diseases with potential applications in modern medicine and healthcare. However, their pharmacological mechanisms, clinical efficacy, and potential synergistic effects with other therapeutic agents remain unclear. Further systematic research is needed to clarify molecular targets and optimize their therapeutic applications. Full article

Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined with antiviral drugs like arbidol, especially for diseases such as Coronavirus disease. This study investigates the synergistic mechanisms between arbidol and components from TQG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro). Methods: We identified compounds from TQG via existing data. Multi-ligand molecular docking, pharmacokinetic/toxicity screening, and preliminary simulations were performed to assess potential synergistic compounds with arbidol. UPLC-Q-Exactive Orbitrap-MS verified the presence of these compounds. Extended simulations and in vitro assays, including Luciferase and surface plasmon resonance, validated the findings. Results: Five compounds interacted with arbidol in synergy based on docking and preliminary dynamics simulation results. Only Baicalein (HQA004) could be identified in the herbal remedy by untargeted metabolomics, with ideal pharmacokinetic properties, and as a non-toxic compound. Extended simulations revealed that HQA004 enhanced arbidol’s antiviral activity via a “Far” Addition Mechanism #2, with an optimal 2:1 arbidol:HQA004 ratio. The movements of arbidol (diffusion and intramolecular conformational shifts) in the system were significantly reduced by HQA004, which may be the main reason for the synergism that occurred. In vitro experiments confirmed an increased inhibition of M^pro by the combination. Conclusions: HQA004 demonstrated synergistic potential with arbidol in inhibiting M^pro. The development of combination therapies integrating Western and herbal medicine is supported by these findings for effective antiviral treatments. Full article