The American journal of the medical sciences最新文献

Background: Long-COVID is defined by persistent symptoms following an initial COVID-19 infection. The normal immune function depends on a precise balance of trace elements, which can provide fresh insights into prospective therapeutic strategies while maintaining oxidative balance and limiting excessive inflammation. Zinc, copper, cobalt, and manganese deficits or excesses can alter the immune system's normal functions and oxidative stress. The study aims to study the trace element profile for predicting long-COVID.

Methods: The levels of serum copper and zinc were measured spectrophotometrically. In contrast, cobalt and manganese were measured using flameless atomic absorption spectrophotometry in 60 long-COVID patients and compared with the 30 controls who had previous SARS-CoV-2 infection but were free from long-COVID symptoms.

Results: Serum levels of copper, cobalt, manganese, and the copper/zinc ratio were considerably elevated in long-COVID patients compared to the control groups. Nonetheless, there was no significant change in zinc levels relative to the control group. The cobalt concentration increases with the duration of the disease and inflammation. Serum manganese level is significantly and negatively correlated with weight. The duration of disease is inversely linked to serum zinc concentrations. There is a substantial correlation between serum copper levels and the period of recovery from acute SARS-CoV-2 infection.

Conclusions: Long-COVID is associated with alterations in serum trace elements (copper, cobalt, and manganese). The imbalances in the trace elements are associated with inflammation, duration of disease, and age. These imbalances may contribute to prolonged symptoms and greater disease severity, suggesting that trace element monitoring could be beneficial in managing long-COVID.

Background: Hypertensive renal disease impacts approximately 753 million individuals worldwide each year. This study evaluates trends in hypertensive renal disease mortality from 1999 to 2020 in the US, focusing on disparities related to gender, race, and urbanization by examining the Age-Adjusted Mortality Rate (AAMR) to inform targeted intervention and improve outcomes.

Methods: The CDC WONDER database analyzed hypertensive renal disease with renal-failure-related mortality from 1999 to 2020, calculating mortality rates and a 95 % confidence interval to assess national trends.

Results: Throughout the study period, males constantly exhibited a higher Age-Adjusted Mortality Rates (AAMR) for hypertensive renal disease with renal-failure-related mortality 148.92 (95 % CI: 148.37 - 149.48) than females 106.11 (95 % CI: 105.73 - 106.49). African American individuals exhibited the highest overall AAMR at 286.29 (95 % CI: 284.68 - 287.9), starting at 186.23 in 1999 (95 % CI: 179.34 - 193.13) and increasing to 529.72 in 2020 (APC: 5.27; 95 % CI: 520.77 - 538.67). From 1999 to 2020, AAMR rose in metropolitan areas from 197.57 (95 % CI: 187.88-207.26) to 1112.12 (APC: 10.00; 95 % CI: 1093.39-1130.85), and in non-metropolitan areas from 97.35 (95 % CI: 90.63-104.08) to 643.06 (APC: 11.81; 95 % CI: 627.76-658.37).AAMRs varied significantly by state, from 61.23 (95 % CI: 59.29-63.16) in Connecticut to 225.06 (95 % CI: 214.96-235.16) in the District of Columbia.

Conclusions: From 1999 to 2020, the mortality rate from hypertensive-related renal diseases rose uncertainly, with a sharp incline starting from 2013 to a sudden surge in 2020 due to COVID-19-related renal complications. Higher deaths were observed in males, African American ethnicity, and individuals living in non-metropolitan areas. Addressing these problems requires a multifactorial public health approach focusing on early detection, equitable care, and targeted intervention to reduce disease burden.

Systemic lupus erythematosus (SLE) is a classic autoimmune condition marked by inflammation in multiple organs and a malfunctioning immune system. Despite advances in immunosuppressive therapies, patients frequently experience relapses, organ damage, and significant quality-of-life impairment. Recent findings indicate that ferroptosis, a form of regulated cell death dependent on iron, has a substantial impact on the progression of lupus. However, the precise molecular interplay between ROS generation, iron metabolism dysregulation, and immune cell dysfunction in SLE remains incompletely understood. This review analyzes the ROS-ferroptosis axis in SLE, highlighting its role in promoting pathological immune responses and worsening tissue injury. It also discusses targeted therapies like iron chelators and GPX4 agonists, which show promise in preclinical models and early trials, identifies actionable targets, evaluates their translational potential for precision therapies, and bridges preclinical mechanisms with clinical applications to address unmet SLE management needs.

Depression is a frequent comorbidity in chronic liver disease (CLD), including Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), viral hepatitis, autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), hemochromatosis, and Wilson's disease. It is associated with worse outcomes, accelerated disease progression, increased hospitalizations, and higher mortality. While antidepressants are commonly prescribed, their effects on liver disease, particularly on liver fibrosis, remain underexplored. This narrative review examines the relationship between depression, CLD, and antidepressants through a literature review of studies published between 2010 and 2024. Some evidence suggests that antidepressants may have antifibrotic properties, as seen in pulmonary fibrosis, but liver-specific data are limited. Understanding their potential role in both mental health and liver disease management could improve patient outcomes. However, significant research gaps remain, and further clinical trials are needed to determine whether antidepressants influence liver fibrosis, disease progression, and overall prognosis in CLD.

Vagus nerve stimulation (VNS) has gained significant attention as a therapy for various medical conditions due to its ability to modulate chronic diseases, pain, and inflammation. VNS delivered by an implanted device is FDA approved for severe epilepsy and refractory depression. VNS delivered with implantable devices or transcutaneous methods are now being studied in several musculoskeletal diseases including osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, and fibromyalgia. VNS activates the neuroimmune axis including the cholinergic anti-inflammatory pathway (CAP), suppressing inflammation and reducing pain. Here, we review the pathophysiology of VNS and the outcomes from clinical trials in musculoskeletal diseases. We address the limitations of these studies, including the inconsistent use of physiological biomarkers, such as heart rate variability, to ensure that VNS is engaging the vagus nerve. More studies are required to reveal the full potential of VNS for pain reduction and disease modification.

Background: Cardiovascular diseases (CVDs) are leading causes of mortality globally, with myocardial ischemia-reperfusion (I/R) injury being a critical challenge in clinical settings. Circular RNAs (circRNAs) have emerged as significant molecular players in various pathophysiological conditions, including myocardial I/R injury.

Objective: This study aimed to investigate the role of circCOL3A1 in myocardial I/R injury and its potential regulatory mechanisms involving miR-29b-3p and MDM2.

Methods: Using a mouse model and H9c2 cardiomyocyte cells, we examined the expression levels of circCOL3A1 under I/R and hypoxia/reoxygenation (H/R) conditions. We utilized RT-qPCR, Western blotting, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and dual-luciferase reporter assays to explore the interaction between circCOL3A1, miR-29b-3p, and MDM2.

Results: CircCOL3A1 was significantly downregulated in both I/R-treated mice and H/R-treated H9c2 cells. Overexpression of circCOL3A1 reduced apoptosis and improved cell viability by modulating the miR-29b-3p/MDM2 axis. These effects were reversed by overexpressing miR-29b-3p or silencing MDM2.

Conclusions: CircCOL3A1 plays a protective role in myocardial I/R injury by acting as a miR-29b-3p sponge, thereby regulating the MDM2-mediated apoptosis pathway. This identifies circCOL3A1 as a potential therapeutic target for treating myocardial I/R injury.

Background: Circular RNAs (circRNAs) are involved in tumorigenesis and the progression of cancer through various pathways. However, the detailed regulatory mechanisms of circRNAs in cervical cancer are not fully understood. The present study was designed to explore the biological functions and potential mechanisms of circCLIP2 (has_circ_0001717) in cervical cancer.

Methods: The expression profiles of circRNAs in cancerous and adjacent normal tissues of cervical cancer patients were examined using RNA sequencing. Gain- and loss-of-function experiments were carried out to determine the biological functions of circCLIP2 in the proliferation, invasion, migration and apoptosis of cervical cancer cells. qRT-PCR was also used to evaluate the expression of circCLIP2, miR-361-3p and STAT2 in cervical cancer cells. The protein levels of STAT2 were determined by western blotting.

Results: CircCLIP2 was identified as the most down-regulated molecule in the cancerous tissues of cervical cancer patients compared to the adjacent normal tissues. Moreover, the levels of circCLIP2 was decreased in cervical cancer patients with metastasis and advanced tumour stage, and patients with high-circCLIP2-expression exhibited poorer survival rate. In addition, over-expression of circCLIP2 suppressed the proliferation, invasion and migration of cervical cancer cells, whereas cell apoptosis was enhanced. Moreover, down-regulated circCLIP2 functioned as the sponge of miR-361-3p, which reduced the expression of STAT2. Furthermore, knockdown of STAT2 inhibited the expression of circCLIP2 at the transcriptional level.

Conclusion: The circCLIP2/miR-361-3p/STAT2 signalling could mediate the progression of cervical cancer. CircCLIP2 may become a novel target for the diagnosis and treatment of cervical cancer.