Life-Basel最新文献

Despite decades of interventions targeting modifiable risk factors to reduce the burden of cardiovascular disease, ischemic heart disease (IHD) remains the leading cause of mortality and the second leading cause of disability-adjusted life-years worldwide. Growing evidence suggests that phthalates-plasticizers widely used in consumer products, cosmetics, and medical devices, and therefore ubiquitous across environmental media, may contribute to IHD development. Epidemiological studies have reported associations between phthalate exposure and multiple markers of atherosclerosis, the pathological hallmark of IHD, with or without mediation by traditional cardiovascular risk factors. Experimental models support these findings, showing that phthalates can induce oxidative stress, mitochondrial dysfunction, apoptosis, lipid accumulation, and epigenetic alterations, all of which promote endothelial damage and atherogenesis. In this review, we synthesize current epidemiological findings linking phthalate exposure to IHD, describe the main cellular and molecular mechanisms involved, and outline research gaps and regulatory perspectives. We also discuss how novel analytical frameworks-including artificial intelligence-may enhance the integration of environmental, clinical, and molecular data to advance risk prediction and prevention strategies.

Gynecologic cancer is a major global health burden, and improvements in screening, surgical techniques, and systemic therapies have significantly prolonged survival. As a result, cardiopulmonary disease has emerged as a leading non-cancer cause of morbidity and mortality among gynecologic cancer survivors. Obesity, which is highly prevalent in this population, substantially increases cardiopulmonary risk by contributing to metabolic syndrome, cardiovascular disease, chronic inflammation, and reduced cardiopulmonary reserve. This narrative review summarizes current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of cardiopulmonary complications in obese patients with gynecologic malignancy. We review the contribution of obesity-related metabolic and endothelial dysfunction, cancer-associated hypercoagulability, and treatment-related toxicities, with particular emphasis on complications arising from surgery, chemotherapy, and radiotherapy. Epidemiologic data demonstrate a markedly increased burden of cardiovascular and pulmonary disease in obese gynecologic cancer patients, including higher rates of myocardial injury, heart failure, venous thromboembolism, and postoperative respiratory complications. Surgical treatment, although central to oncologic management, imposes substantial cardiopulmonary stress, placing obese patients at heightened perioperative risk. Future studies should focus on preoperative risk stratification, optimization of obesity-related comorbidities, and multidisciplinary perioperative management, including enhanced recovery pathways, as well as appropriate use of high-dependency or intensive care monitoring to reduce morbidity and improve both oncologic and long-term non-oncologic outcomes in this population.

Background: Environmental agents can disrupt thyroid function at several levels, including the synthesis, action, and excretion of thyroid hormones, and an inadequate concentration of thyroid hormones affects almost all organs and systems.

Objective: The present study aimed to evaluate the histology and presence of the cytokines TNFα, IL-6, and IL-10 in the thyroid gland by immunohistochemical labeling, as well as the body weight and craniocaudal length of pups of Wistar rats exposed to ambient air in the vicinity of the Capuava Petrochemical Complex (CPC), located in the Santo André and Mauá cities, at São Paulo State, Brazil.

Methods: This study used Wistar rats between 14 and 16 weeks of age, distributed in couples, that were exposed to pollution from the CPC located in the regions of Santo André and Mauá, Sao Paulo State, Brazil. One couple was positioned 600 m (SS1), and another was 1000 m (SS2) from the CPC, while the control group was kept at the animal research facility of the Physiology Laboratory of the FMABC University Center, Santo André. After mating, the resulting offspring were monitored for four weeks, with their body weight and craniocaudal length measured weekly. Subsequently, the offspring's thyroid glands were histologically analyzed using H&E staining and immunohistochemistry to detect the presence of inflammatory cytokines (TNF-α, IL-6, and IL-10).

Results: In the SS1 group, the thyroid glands showed follicular heterogeneity with macrofollicles and numerous microfollicles without colloid, lined by flattened epithelial cells. In these thyroid follicles, there was intense TNFα (p = 0.002) staining, slight IL-6 staining (p = 0.042), and significantly stronger staining for IL-10 (p = 0.013) compared to that in the control group. This group also had a significantly lower body weight than the control animals on the 6th, 13th, and 20th days of life. In the SS2 group, the thyroids presented an architecture dominated by microfollicles without colloid as well as inflammatory cells in the colloid of some follicles. Immunohistochemistry revealed intense pan-follicular TNFα (p = 0.002) staining, with additional cytoplasmic staining of IL-6 (p = 0.040) and IL-10 (p = 0.006). The SS2 group also showed a more pronounced deficit compared to the SS1 group in terms of birth weight. The cranial-caudal length was shorter on the 13th and 20th days of life in the SS1 and SS2 groups compared to the control group.

Conclusions: The results indicate that proximity of rats to the CPC was a determining factor in the development of histological abnormalities and increases in inflammatory cytokine markers in the thyroid glands of the offspring. In addition, the offspring born near the CPC had lower birth weights and shorter craniocaudal lengths compared to the animals in the control group.

Malaria has long been a significant global health concern, listed as a high-priority disease by several global health agencies, despite of several control measures have been put in place. Most widely utilized treatment options for malaria include chloroquine, artemisinin-based combination therapy (ACT), and quinine. However, challenges, such as drug resistance, misdiagnosis, and limited treatment efficacy remain major concerns. Despite ongoing efforts, the development of an effective malaria vaccine is still debatable. Many existing malaria treatments have drawbacks, such as low water solubility, poor bioavailability, and a rise in drug-resistant parasites owing to their non-judicious use, which contributes to increased malaria cases and fatalities. Nanotechnology presents a promising approach to safer and more effective malaria therapy and control. Nanoparticles offer several advantages over conventional treatments, including high drug-loading capacity, targeted delivery, improved biocompatibility, and reduced toxicity in host cells. Green nanotechnology-based antimalarial therapies have demonstrated potential therapeutic benefits, enhanced safety, and cost-effectiveness compared to traditional treatments, ultimately improving patient compliance and treatment outcomes. In this review paper, we discussed non-conventional breakpoints in the malarial life cycle, traditional herbal remedies for malaria, and nanoparticle-based delivery systems. Additionally, we reviewed the antimalarial effects of herbal nano-formulations, their pharmacological and therapeutic potential, drug-resistant malaria, preventive strategies, vector control using green nanomaterials, and the challenges associated with plant-based nanotechnologies. This review suggests nanotechnology-based therapeutics as promising candidates to treat malaria with significant room for applications and commercialization potential in the longer run.

Background: Clozapine (CLZ) is an atypical antipsychotic mainly prescribed for treatment-resistant schizophrenia. Beyond psychotic symptoms, patients often exhibit persistent cognitive impairments across domains such as attention, learning, and memory. The mechanisms by which CLZ may influence cognition and provide neuroprotection are not fully elucidated. Accordingly, this study examined how CLZ modulates lipopolysaccharide (LPS)-induced neurotoxicity in rats.

Method: Rats were administered LPS to induce cognitive impairment and subsequently treated with CLZ. Behavioral assessments were performed using maze tests (elevated plus-maze (EPM), novel object recognition (NOR), and Y-maze). Biochemical analyses included cholinergic function (acetylcholine (ACh)), neurodegeneration-associated enzymes (glycogen synthase kinase-3 beta (GSK-3β), β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), and dipeptidyl peptidase-4 (DPP-4)), oxidative stress markers (lipid Peroxidation (LPO), catalase, and reduced glutathione (GSH)), and apoptotic proteins (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved Caspase-3 (c-Caspase-3)).

Results: CLZ treatment markedly improved performance in EPM, NOR, and Y-maze tasks, indicating recovery of cognitive function in LPS-exposed rats. At the molecular level, CLZ enhanced ACh levels, upregulated the anti-apoptotic protein Bcl-2, and restored antioxidant defenses (catalase and GSH). Conversely, CLZ reduced LPS-induced neurotoxicity by lowering GSK-3β activity, LPO, and pro-apoptotic markers (Bax and c-Caspase-3).

Conclusion: The findings demonstrate that CLZ exerts neuroprotective effects in an LPS-induced rat model, improving cognition through modulation of cholinergic transmission, oxidative stress, and apoptosis pathways. These results clarify key mechanistic pathways through which CLZ may exert cognitive benefits and highlight its potential relevance for improving schizophrenia-related cognitive dysfunction. Further molecular studies are warranted to confirm and extend these observations toward clinical translation.

5-Aminolevulinic acid (5-ALA) is a naturally occurring heme precursor with a favorable safety profile and is widely used for fluorescence-guided resection of malignant gliomas. Exogenous administration of 5-ALA results in the selective intracellular accumulation of protoporphyrin IX (PpIX), predominantly within tumor cell mitochondria, reflecting tumor-specific alterations in cellular metabolism and heme biosynthetic pathways. Historically, the radiosensitizing potential of 5-ALA was considered limited, as 5-ALA itself is not a porphyrin and intracellular PpIX levels are lower than those achieved with classical porphyrin-based agents, such as hematoporphyrin derivatives or porfimer sodium. Recent experimental and translational studies have challenged this view by demonstrating that the interactions between 5-ALA-induced PpIX and ionizing irradiation elicit biologically significant antitumor effects. This emerging concept has been termed radiodynamic therapy (RDT) and represents a therapeutic paradigm distinct from conventional DNA-centered radiosensitization. Accumulating evidence suggests that 5-ALA-based RDT induces mitochondria-centered oxidative stress through both immediate and delayed reactive oxygen species generation, thereby linking metabolic vulnerability to the radiation response. In this review, we summarize the current mechanistic insights into 5-ALA-based RDT, particularly mitochondrial dysfunction and oxidative stress amplification. We also discuss the translational implications and future perspectives for integrating 5-ALA-based RDT into multimodal treatment strategies for malignant gliomas.

Conventional measures such as maximal oxygen uptake (V˙O₂max), although widely regarded as the gold standard, do not fully capture endurance performance. Therefore, this study investigated whether a 2.4 km Cooper test elicits measurable changes in blood-based biomarkers (decorin, hypoxanthine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), brain-derived neurotrophic factor (BDNF)) and whether integrating these markers may improve performance prediction in a heterogeneous sample of runners. In this cross-sectional observational proof-of-concept study, thirty-three participants completed the 2.4 km Cooper test, with venous blood samples collected at baseline and post-test. Non-parametric statistical tests were used to assess biomarker changes (α = 0.05), with exploratory correlations evaluated using Spearman's ρ. To examine whether blood-based biomarkers provide information beyond conventional field-based predictors, Ridge regression with leave-one-out cross-validation (LOOCV) was applied to predict 10 km race time in a subsample of 24 participants who completed a 10 km race two weeks later. The Cooper test elicited significant post-test changes in decorin, hypoxanthine, and BDNF (all p < 0.001). Higher post-test decorin (ρ = -0.44, p = 0.010) and hypoxanthine (ρ = -0.37, p = 0.034) were associated with faster Cooper test performance. In Ridge regression analysis, adding post-test decorin to conventional predictors resulted in a minor reduction of 10 km race time prediction error. This study suggests that decorin may provide complementary information to a conventional field-based test in heterogeneous recreational runners. Post-test decorin marginally contributed to 10 km race performance prediction beyond established predictors, though external validation and comparison with directly measured V˙O₂max are needed before practical application can be recommended.

Background: Cardiac arrhythmias are a frequent complication of acute SARS-CoV-2 infection. However, their long-term prevalence and clinical determinants among patients with post-COVID-19 syndrome, especially those previously hospitalized, remain poorly defined.

Objectives: To assess the prevalence and types of arrhythmias in long COVID patients following hospitalization and to identify associated clinical risk factors.

Methods: In this cross-sectional study, 53 patients previously hospitalized with confirmed COVID-19 were evaluated ≥3 months post-infection. All participants underwent a standardized clinical assessment, 12-lead electrocardiography, and 24 h Holter monitoring. Logistic and Cox regression analyses were performed to identify predictors of arrhythmia.

Results: Arrhythmias were identified in 41.5% (n = 22) of patients. Atrial fibrillation (32%) was the most frequent arrhythmia, followed by sinus bradycardia (27%) and sinus tachycardia (18%). Age (OR 1.06, 95% CI 1.01-1.10, p = 0.01) and length of hospital stay (OR 1.1, 95% CI 1.01-1.2, p = 0.04) were independently associated with arrhythmia. Biguanide (metformin) therapy was inversely associated with the occurrence of arrhythmia (Exp(B) = 0.017, p = 0.008). Dyspnea (82.4%) and palpitations (41.5%) were the most commonly reported symptoms.

Conclusions: Arrhythmias are common in patients with long COVID following severe disease. Advanced age and prolonged hospitalization are significant risk factors, while biguanide use may offer a protective effect. These findings underscore the need for targeted cardiac surveillance in this population.

Partial anomalous pulmonary venous return (PAPVR) with dual drainage is a very rare congenital heart anomaly. We report the case of a 6-year-old boy with PAPVR in whom both upper pulmonary veins (PVs) drain anomalously into the systemic venous circulation, while maintaining preserved intrapulmonary collateral venous connections with the remaining pulmonary veins draining into the left atrium. Careful balloon occlusion testing of the anomalous PVs was performed, simultaneously with measurements of pulmonary pressures and control angiography, proving the absence of venous congestion in the upper lung fields during the pulmonary venous phase. Transcatheter occlusion using vascular plugs was safely and successfully performed.

Osteoarthritis is associated with chronic inflammation, which contributes to a hypercoagulable state. Oxidative stress may further disrupt homeostatic balance, thereby promoting thrombotic events. This study evaluated the association between biomarkers of oxidative stress, inflammation, haemostasis, and bone metabolism in patients with spinal osteoarthritis. A total of 48 patients were included. The levels of inflammatory, bone turnover, haematological, and coagulation biomarkers were determined using standard laboratory methods. Redox status was assessed via prooxidant-antioxidant balance (PAB) and superoxide dismutase (SOD) activity. Patients with elevated PAB showed significantly higher erythrocyte sedimentation rate (ESR) (p = 0.005), alkaline phosphatase (ALP) (p = 0.003) and fibrinogen levels (p = 0.006) and platelet count (p = 0.040), along with lower 25-OH vitamin D levels (p = 0.045) and shortened PT (p = 0.008) and aPTT (p = 0.017). In low oxidative stress states (PAB < 100 U/L), significant correlations were observed among redox, coagulation, and bone turnover markers, whereas in high oxidative stress (PAB ≥ 100 U/L), it was characterised by predominant associations between redox and bone turnover biomarkers. Patients with grade V disc degeneration had a significantly higher probability of elevated D-dimer levels compared to those with grade IV (OR = 5.440; p = 0.009). In addition, elevated D-dimer levels were associated with increased ESR (p = 0.015), IL-6 (p = 0.016) and ALP levels (p = 0.034). The associations between biomarkers of redox status, inflammation, coagulation and bone turnover are influenced by the extent of oxidative stress. Our results suggest that PAB and D-dimer may serve as potential biomarkers for disease severity and thrombotic risk. Further studies are needed to confirm these preliminary findings.