Current Pharmaceutical Design - Online First

This research aimed to reveal the role of antioxidants and DNMT1 gene expression in behavioral disorders after exposure to stress.

Forty-eight male and female mice (weight 25-35 grams) were used. Their pups (weight 18-22 grams) were divided into 6 groups (n=20), Control, Social isolation stress (SIS), and SIS + N-acetylcysteine (NAC) 150 mg/kg intraperitoneally for male and 3 similar groups for female subjects, eight mice from each group were used for the first-generation experiments and another for mating and producing the second generation. The second-generation pups were designated into 9 groups A to I. After conducting behavioral tests of the Morris water maze (MWM) and shuttle box, they were anesthetized, decapitated, and their brains were removed. The neuronal counts of CA1 and CA3 were performed. DNMT1 gene expression, total antioxidant capacity (TAC), and malondialdehyde (MDA) of the brain were measured.

Spatial memory, passive avoidance, and TAC decreased in the SIS groups. MDA and DNMT1 gene expression of the SIS groups increased (p<0.001). Dead neurons in the CA1 and CA3 regions increased in the SIS group (p<0.001).

According to the results of this study, N-acetylcysteine enhanced learning and memory while reducing neuronal death by decreasing oxidative stress. Additionally, it lowered the expression of the DNMT1 gene, which plays a crucial role in DNA methylation.

After studying the human population, N-acetylcysteine may be introduced as an adjunct therapy to help mitigate the effects of stress.

Qiangjie Xinyi Decoction (QJXYD) has been effectively utilized in the clinical treatment of Northwest Dryness Syndrome (NDS) with allergic rhinitis (AR). However, its therapeutic effect lacks a theoretical basis. This study employs network pharmacology and experimental validation to investigate the therapeutic potential of QJXYD on NDS with AR and elucidate its mechanism of action.

Databases such as TCMSP, OMIM, Genecards, etc. were used to obtain relevant targets for traditional Chinese medicine and diseases. A protein interaction network (PPI) was constructed in the STRING database to screen the core targets of QJXYD for the prevention and treatment of AR. A drug-disease-pathway network diagram was constructed using Cytoscape 3.9.0 to identify the main active ingredients that exert efficacy. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using the DAVID database. The significant findings were subsequently validated through molecular dynamics simulations. An NDS was established with the AR model in rats, and the network pharmacology results were validated through in vivo experiments.

The key targets screened for PPI network construction included IL-6, TNF, VEGFA, etc. Key components such as quercetin, luteolin, and beta-sitosterol were explored in the component target pathway network diagram. GO functional enrichment mainly involved protein binding, inflammatory response, and other functions. KEGG enrichment analysis included pathways such as Th17 cell differentiation and the HIF-1 signaling pathway. Molecular docking and molecular dynamics simulations validated the research results. Animal experiments showed that QJXYD can reduce the protein and gene expression of IL-6, TNF, and VEGFA in the nasal mucosal tissue of NDS with AR rats.

This study, utilizing network pharmacology and animal experiments, found that QJXYD may target IL-6, TNF, and other targets through components such as quercetin, thereby regulating inflammation-related pathways to treat AR. Animal experiments confirmed that it can reduce the expression of key targets in the nasal mucosa. The research system revealed the mechanism of the compound, but there are limitations, such as unverified predictions and insufficient clinical representativeness of the model, which require further research.

QJXYD can treat NDS with AR through multiple components, targets, and pathways, providing a theoretical basis for further research.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths globally. Traditional treatments face limitations like low effectiveness, poor specificity, and significant side effects. Gene therapy, particularly siRNA-based, is promising for targeted gene regulation but requires effective delivery systems due to the instability and poor target delivery of unmodified siRNA.

This study examined the storage and biological stability of LP-PEI-SPION (LPS) and GPC3-LP-PEI-SPION (GLPS). The potential of these agents as tumor imaging contrast agents and the targeting ability of gene delivery carriers were assessed through ex vivo organ fluorescence imaging and in vivo tumor magnetic resonance imaging (MRI). Antitumor efficacy was evaluated through tumor volume, protein blotting, immunohistochemistry, and TUNEL assays. In vivo safety was evaluated using HE staining, nude mouse weight changes, and blood biochemical indicators.

LPS and GLPS both formed stable siRNA complexes. GLPS showed excellent tumor targeting in vivo. MRI results showed that the GPC3-targeting peptide effectively enhanced the MR imaging performance and diagnostic accuracy. Tumor volume and weight measurements demonstrated potent tumor inhibition by GLPS/siRNA. Immunoblotting and immunohistochemistry revealed significant GPC3 reduction in the GLPS/siRNA-targeted group. Safety evaluations confirmed good biocompatibility for both LPS/siRNA and GLPS/siRNA.

GLPS/siRNA demonstrates superior in vitro transfection and anti-tumor efficacy compared to LPS/siRNA. It exhibits high tumor fluorescence signals, reduced MRI T2 relaxation time, and effective tumor enrichment, providing MRI imaging capability. Safety assessments, including HE staining, body weight, and blood biochemistry, indicate good biocompatibility. The development of siRNA-based therapeutics has progressed, yet challenges remain, such as siRNA's susceptibility to degradation and poor membrane permeability. While carriers like liposomes and polymers are used, they have limitations. Nanoparticles that enhance endosomal/lysosomal escape and promote cytoplasmic siRNA release are needed to improve delivery efficiency, reduce off-target effects, and enhance safety.

GLPS/siRNA demonstrates good stability, tumor targeting, imaging capability, and antitumor efficacy with favorable safety, positioning it as a promising theragnostic platform for HCC. This integrated system provides novel clinical tools for diagnosis and treatment, establishes a foundation for clinical translation, and enables simultaneous tumor imaging and gene therapy—offering innovative strategies for combined tumor theranostics.

The delivery of healthcare services via information and communication technology, or telemedicine, has grown to be an essential part of modern medicine. This study explores the evolving role of telemedicine, focusing on its expansion into the Metaverse, and evaluates its potential to improve healthcare accessibility, patient engagement, and medical outcomes.

A comprehensive analysis of the literature was conducted, evaluating studies investigating the efficacy of telemedicine in different medical fields, notably mental health, chronic disease management, and post-surgical follow-ups. This study assessed the impact of emerging technologies, specifically virtual reality (VR) and augmented reality (AR), on telemedicine, emphasizing their applications within the Metaverse. Furthermore, ethical considerations, insurance limitations, and technological disparities were assessed.

Telemedicine has significantly enhanced healthcare access, especially in remote and underserved regions. Patient satisfaction and purpose to continue with telemedicine services are elevated, particularly in specialized areas like Tele-stroke and mental health counseling.

The Metaverse has the potential to transform telemedicine through the establishment of immersive and interactive healthcare settings. VR and AR have the potential to facilitate virtual consultations, enhancing the interaction between patients and healthcare professionals. Additionally, the integration of data may lead to improvements in diagnostic accuracy and treatment planning. However, issues such as data privacy, cybersecurity hazards, and the digital gap must be addressed to provide adequate access.

Telemedicine has demonstrated significant utility within modern healthcare, and its incorporation with the Metaverse offers novel prospects for improving patient care, advancing medical education, and facilitating collaborative research. Despite the promising benefits, it is crucial to address technological, ethical, and regulatory challenges to ensure widespread adoption and successful implementation.

Increasing anion gap (AG) correlates with both short- and long-term mortality in intensive care unit (ICU) patients with acute kidney injury (AKI). However, the relationship between AG fluctuations and AKI prognosis has been understudied. This study aims to evaluate the predictive value of AG fluctuations within the first 48 hours after ICU admission for renal recovery and 30-day all-cause mortality in AKI patients.

Data were extracted from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2) database, including AKI patients aged 18 and older. A multifactorial Cox regression model was employed to assess the impact of AG fluctuations within 48 hours of ICU admission on mortality, adjusted using five models. Kaplan-Meier survival curves and curve-fitting analysis were used to illustrate the relationship between AG fluctuations and mortality risk.

A total of 15,438 patients with AKI were included, 57.0% of whom were male. The 30-day all-cause mortality rate was 19.19%. Patients were categorized into three groups based on AG fluctuations within the first 48 hours: <3 mmol/L, 3-5 mmol/L, and >5 mmol/L. Cox regression and survival analysis indicated a significantly higher 30-day mortality rate in the >5 mmol/L group (HR = 1.63; 95% CI = 1.50-1.77, P < 0.001), with the worst prognosis. Restricted cubic spline analysis revealed a nonlinear relationship between AG fluctuations and 30-day mortality risk.

The findings suggest that AG fluctuations during the first 48 hours of ICU admission are closely associated with adverse outcomes in AKI patients. Monitoring AG dynamics may aid clinicians in identifying high-risk patients and enhancing patient management by allowing for timely interventions that may improve prognosis.

AG fluctuations within the first 48 hours of ICU admission are a key predictor of renal recovery and 30-day mortality in AKI patients. AG fluctuations greater than 5 mmol/L are significantly associated with increased mortality risk.