Biomolecules & biomedicine最新文献

Massive hemoptysis is a life-threatening complication in patients with advanced primary lung cancer, and effective, safe treatments are crucial. This study aimed to investigate the efficacy and safety of CalliSpheres drug-eluting bead bronchial arterial infusion chemoembolization (DEB-BACE) for managing this condition. A retrospective analysis included 144 patients with advanced primary lung cancer and massive hemoptysis treated at multiple hospitals from January 2019 to January 2023. Patients undergoing bronchial artery embolization were divided into two groups: the observation group (n=76) received CalliSpheres DEB-BACE with epirubicin, and the control group (n=68) received 8spheres blank embolization. Both groups achieved successful hemostasis, with no statistically significant difference in success rates (observation group: 88.16%, control group: 86.76%). However, the observation group had a significantly longer median duration without hemoptysis (96 days vs. 50 days). Two months post-therapy, the observation group showed higher objective response rates (82.89% vs. 38.24%) and disease control rates (92.11% vs. 66.18%) compared to the control group. Adverse reactions were manageable and similar between groups, with no serious complications observed. By January 31, 2024, the observation group had significantly longer median overall survival (11 months vs. 7 months). The DEB-BACE treatment demonstrates safety and efficacy in managing massive hemoptysis in patients with advanced lung cancer. However, the superiority of this approach over bland embolization remains to be established through well-designed prospective studies. Future research is anticipated to provide a definitive comparison and further validate the role of DEB-BACE in clinical practice.

Multiple studies have been published regarding various nutritional supplements or interventions to improve chronic pain. However, many of these studies emphasized widespread pain and were not specific to the spine. Therefore, the primary objective of this scoping review was to evaluate available evidence related to nutritional supplementation or dietary strategies for spine-related pain. A comprehensive literature search was performed on October 11, 2022, and updated on May 2, 2024. Databases included: MEDLINE (PubMed), Embase, Cochrane Library, Scopus, and Web of Science. Results were limited to those published within the past 10 years, to English-language articles, and excluded animal studies. Of the 2,081 screened articles, 29 were included in the final review. Of these, 26 focused on the low back, one on the neck, and two referred to generalized "back" pain. The largest number of studies were found on vitamins D and B, specifically for low back pain. However, there were conflicting findings for both vitamins; therefore, further research is necessary before these can be confidently recommended to patients suffering from low back pain. Furthermore, this scoping review identified a lack of consistency in study design, population or sample size, and outcome measures among currently published studies with a primary focus on nutritional supplementation or dietary strategies for spine-related pain.

To investigate the prognostic value of GPN1 in cancer and its role in the migration of hepatocellular carcinoma (HCC or LIHC) cells, we used several databases to assess GPN1 expression levels and effects in human tumors. Furthermore, experiments were conducted to verify changes in GPN1 expression in HCC cell lines and explore its biological function. We found that GPN1 gene and protein expression were significantly increased in several tumor tissues. Higher GPN1 expression was associated with unfavorable overall survival. Additionally, there was a strong association between GPN1 expression and several clinicopathological features, according to multivariate Cox regression analysis. Moreover, GPN1 gene mutation and methylation were present in some tumors. A relationship was also found between GPN1 expression and immune infiltration. Notably, immune checkpoint analysis showed that GPN1 expression was correlated with PD-1/PDL-1 and CTLA-4, suggesting it may serve as a biomarker for predicting immune subtypes and response to immunotherapy in HCC. Enrichment analysis in HCC indicated that GPN1 is primarily involved in RNA metabolism. Additionally, drug sensitivity analysis revealed that GPN1 appeared to be responsive to 16 drugs. Finally, GPN1 upregulation was confirmed to promote the migration of HCC cells. This study provides a comprehensive overview of GPN1 in human cancer and demonstrates that GPN1 contributes to the migration of HCC cells, potentially serving as a prognostic and immunotherapy biomarker.

Sleep disorders are among the common comorbidities of autism spectrum disorder (ASD), which not only affect the daily life and learning ability of children but may also exacerbate other symptoms of ASD, seriously impacting the quality of life of children and their families. Given this, understanding the neurobiological mechanisms of sleep disorders in children with ASD has significant research value for developing effective intervention strategies. Melatonin, 5-HT, and orexin are key neurotransmitters that regulate the sleep-wake cycle. Through in-depth analysis of the biological functions and regulatory pathways of these neurotransmitters, new perspectives may be provided for personalized treatment of sleep disorders in children with ASD. This article reviews the research progress on melatonin, 5-HT, and orexin in sleep disorders among children with autism spectrum disorder, focusing on exploring the mechanisms of these key neurotransmitters in sleep disorders of children with ASD and how they affect the sleep-wake cycle, providing a theoretical basis for improving the sleep quality of children with ASD.

Inflammation and coagulation cascades are closely correlated with cancer occurrence and progression. This study investigated the prognostic value of the combination of plasma fibrinogen level and neutrophil-to-lymphocyte ratio (F-NLR) in patients with upper tract urothelial carcinoma (UTUC). The predictive ability of the F-NLR for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) was initially established and then further validated in patients who underwent radical nephroureterectomy (RNU) for UTUC. As a result, patients were divided into three groups following the establishment of cut-off values for the neutrophil-to-lymphocyte ratio (NLR) (≥2.53 vs <2.53) and fibrinogen (≥4.55 vs <4.55) through receiver operating characteristic (ROC) curve analysis: F-NLR score 0 (low fibrinogen and low NLR), 2 (high fibrinogen and high NLR), or 1 (remaining patients). The F-NLR score was then identified as an independent risk factor for OS, CSS, and PFS (all P value <0.05) by multivariate regression analysis in both the training and validation cohorts. In addition, F-NLR-based nomograms for OS, CSS, and PFS were developed and evaluated using the concordance index (C-index) and calibration curves. The integration of the F-NLR into existing nomograms improved predictive accuracy compared to the use of nomograms without the F-NLR score. This suggests that the addition of F-NLR is beneficial for enhancing the accuracy of prognosis prediction in patients with UTUC. The F-NLR score may serve as a powerful predictor for patients with UTUC.

Lactate dehydrogenase (LDH), a nonspecific inflammatory biomarker, has been used in the assessment of acute myocardial infarction, acute hepatitis, acute lung injury, and other severe diseases. However, no studies have evaluated the prognostic value of LDH in patients with non-traumatic intracerebral hemorrhage (ICH). This cohort study aims to assess the association between LDH levels and 28-day all-cause mortality in patients with non-traumatic ICH. Data for this retrospective cohort analysis were obtained from the MIMIC-IV (v2.2) database, and the study included patients with non-traumatic ICH as defined by the International Classification of Diseases, 9th and 10th editions. Patients were categorized into four distinct groups based on their LDH levels. The primary outcome of interest was the 28-day mortality rate. To analyze these associations and assess the consistency of interactions, subgroup analyses, Cox regression analysis, Kaplan-Meier (KM) curves, and nonlinear analysis were conducted. A total of 406 patients with non-traumatic ICH were enrolled in the study and were divided into quartiles based on LDH levels. The KM curve indicated that the 28-day all-cause mortality rate of patients in the Q4 group (LDH > 287.25) was significantly higher than in the Q1 (LDH < 194.7) (P < 0.001) and Q2 (194.7 < LDH < 233.0) (P < 0.001) groups, though not significantly different from Q3 (P = 0.140). Multivariate Cox proportional hazards analysis revealed that patients in the highest LDH quartile had a significantly increased risk of mortality compared to those in the lowest quartile across three models: unadjusted [HR, 3.401; 95% CI, 1.719-6.731; P < 0.001], partially adjusted [HR, 2.422; 95% CI, 1.211-4.846; P = 0.012], and fully adjusted [HR, 3.054; 95% CI, 1.522-6.126; P = 0.002]. Restricted cubic spline (RCS) models revealed an L-shaped association between LDH levels and the 28-day all-cause mortality rate, indicating a non-linear relationship (P < 0.001). No significant interactions were observed between LDH levels and other factors in the subgroup analyses (all P for interaction > 0.05). Our findings indicate a significant association between 28-day all-cause mortality and LDH levels in patients with non-traumatic intracerebral hemorrhage. Specifically, patients with elevated LDH levels within the first 24 hours of ICU admission are at a higher risk of mortality.

In this study, we established and validated a competing risk nomogram for predicting the cumulative incidence of cervical adenosquamous carcinoma (ASC)-specific death in patients undergoing radical hysterectomy. Patients diagnosed with ASC between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) for various variables influencing ASC-specific mortality was computed. A Fine-Gray competing risk model was used to identify independent predictors, formulating a competing risk nomogram. A multivariate Cox proportional hazards model was also applied for comparative analysis. The performance of the nomogram was assessed using metrics such as the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A corresponding risk classification system was constructed based on nomogram-derived scores. Factors such as advanced age, racial background (Black race), higher tumor grade, increased tumor size, advanced TNM stage, and receipt of radiotherapy without chemotherapy were found to be positively associated with elevated ASC-specific mortality. Additionally, age, T stage, M stage, and chemotherapy were identified as independent predictors correlated with ASC-specific mortality. The established nomogram exhibited accurate discriminatory capabilities and superior net benefits compared to the traditional TNM staging system. Additionally, the high-risk group consistently demonstrated higher probabilities of ASC-specific death in both the training and validation sets. The developed nomogram proficiently quantified the incidence of ASC-specific death in patients subjected to radical hysterectomy for ASC. This tool could help clinicians in formulating personalized treatment strategies and devising follow-up protocols.

Cancer remains a leading cause of mortality, with non-small cell lung cancer (NSCLC) being a primary contributor to cancer-related deaths. Traditional treatment strategies such as chemotherapy, radiation, and hormone therapy often present challenges, including severe side effects, drug resistance, and toxicity. Recent advancements in nanotechnology aim to enhance the effectiveness of cancer therapies by targeting drugs selectively and specifically to tumor cells. Among these innovations, exosomes, or small extracellular vesicles (sEVs), have emerged as promising carriers for drug delivery due to their natural origin and ability to encapsulate both small molecules and biologics. This study explores the use of exosomes derived from camel milk in Hail, Saudi Arabia, as a vehicle for delivering curcumin (CUR), a polyphenol with known chemopreventive properties but limited bioavailability. Camel milk was processed to isolate exosomes through differential centrifugation, followed by characterization using dynamic light scattering, zeta potential measurements, and Western blot analysis to confirm exosomal markers. The encapsulation of CUR into camel milk-derived exosomes demonstrated a 20% loading efficiency as analyzed by UPLC. In vitro antiproliferative assays revealed that the exosomal formulation of CUR (ExoCUR) significantly enhanced cytotoxicity against drug-sensitive (A549) and taxol-resistant (A549TR) lung cancer cells compared to free CUR. Molecular docking studies and molecular dynamics simulations indicated that CUR has a strong binding affinity for the epidermal growth factor receptor (EGFR), comparable to the established drug gefitinib. Furthermore, CUR effectively downregulated EGFR and STAT3 expression in lung cancer cells, suggesting its potential to disrupt key signaling pathways involved in tumor progression. Our findings highlight the potential of camel milk-derived exosomes as an effective and biocompatible delivery system for CUR, offering a promising strategy to overcome the limitations of current cancer therapies and enhance the therapeutic efficacy of chemopreventive agents.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

Hypertension is a prevalent cardiovascular disease. Exercise is widely recognized as an effective treatment for hypertension, and it may also influence the composition of the intestinal microflora. However, it remains unclear whether exercise can specifically regulate the intestinal microflora in the context of hypertension treatment. In this study, tail blood pressure in spontaneously hypertensive rats (SHR) was measured using a blood pressure meter after exercise intervention and fecal bacteria transplantation following exercise. Blood lipid levels were assessed using an automatic biochemical analyzer, and 16S rRNA sequencing was employed to analyze the intestinal microflora. Histological examinations of ileal tissue were conducted using HE and Masson staining. Intestinal permeability, inflammatory status, and sympathetic activity were evaluated by measuring the levels of diamine oxidase, D-lactic acid, C-reactive protein, interleukin-6, tumor necrosis factor-α, lipopolysaccharide, norepinephrine, angiotensin II, cyclic adenosine monophosphate, and cyclic guanosine monophosphate. Exercise was found to reduce blood pressure and blood lipid levels in SHR. It also improved the composition of the intestinal microflora, as evidenced by a reduced Firmicutes/Bacteroidetes ratio, an increase in bacteria that produce acetic and butyric acid, and higher Chao 1 and Shannon diversity indices. Furthermore, exercise reduced the thickness of the fibrotic and muscular layers in the ileum, increased the goblet cell/villus ratio and villus length, and decreased intestinal permeability, inflammatory markers, and sympathetic nerve activity. The intestinal microbial flora regulated by exercise demonstrated similar effects on hypertension. In conclusion, exercise appears to regulate the intestinal microflora, and this exercise-induced change in flora may contribute to improvements in hypertension in rats.