Biomolecules & biomedicine最新文献

Ferroptosis plays a crucial role in the secondary pathophysiological damage to brain tissue surrounding hematomas after intracerebral hemorrhage (ICH). While platelet factor 4 (PF4) is known to promote regeneration following peripheral nerve injury, its role in brain tissue repair after cerebral hemorrhage remains unclear. In this study, Hemin-induced PC12 cells were treated with various inhibitors and assessed for viability, oxidative stress, and ferroptosis using a combination of assays, including CCK-8 (Cell Counting Kit-8), EdU (5-Ethynyl-2’-deoxyuridine), flow cytometry, and immunofluorescence. ICH cells were also treated with recombinant PF4 (Rm-PF4) and a CXCR3 antagonist (AMG487) to investigate the mechanism by which Rm-PF4 influences Hemin-induced PC12 cell injury and inflammation. Subsequently, ICH mouse models were established via collagenase injection. Neurological function in these mice was evaluated using the Cylinder and Corner tests. Histopathological damage to brain tissue was analyzed through HE, TUNEL, and Nissl staining, as well as immunohistochemistry, to further explore the role of Rm-PF4 in controlling neuroinflammation in vivo. Results showed that Rm-PF4 inhibited Hemin-mediated ferroptosis-induced PC12 cell damage and inflammation by activating the CXCR3/AKT1/SLC7A11 signaling pathway. Blocking the CXCR3/AKT1/SLC7A11 pathway partially reversed PF4's protective effects on Hemin-induced PC12 cells. In ICH mice, pro-inflammatory marker CD16 (3rd day) and anti-inflammatory marker Arg1 (7th day) were significantly decreased and increased, respectively (p<0.05). IL-6, TNF-α, and IL-1β levels were down-regulated in brain tissues after Rm-PF4 injection, which was significantly reversed by AMG487. PF4 inhibits ferroptosis after ICH reduced PC12 cell damage and the inflammatory response via activating the CXCR3/AKT1/SLC7A11 pathway.

Hyperoside (HYP) exhibits diverse pharmacological effects and holds potential for enhancing chemotherapy sensitivity. However, few studies have reported the impact of HYP on the malignant progression of esophageal carcinoma (EC) and its sensitivity to radiotherapy. The impact of HYP on the viability of EC cells (TE-1 and KYSE-150) was assessed using Cell Counting Kit-8 (CCK-8) assays. The biological characteristics and radiosensitivity of EC cells following HYP treatment were evaluated through clone formation experiments, flow cytometry, scratch wound-healing assays, and transwell migration and invasion assays. Western blot analysis was performed to determine the levels of proteins associated with cell death and epithelial-mesenchymal transition (EMT), as well as to explore whether HYP interferes with the radiosensitivity of EC cells via the  STAT3/AKT/ERK pathways. Finally, a subcutaneous graft tumor model was constructed to investigate the effects of HYP and X-ray treatments on in vivo tumor growth. The findings indicated a dose-dependent decrease in the survival rate of KYSE-150 and TE-1 cells following HYP treatment. HYP treatment also inhibited cell proliferation, invasion, migration, and EMT, while increasing the apoptotic rate and radiosensitivity of the cells. Notably, HYP suppressed the malignant progression of EC and enhanced radiosensitivity via the STAT3/AKT/ERK pathway. Moreover, HYP impaired the growth of EC tumors in mice, with the combined HYP and X-ray treatment exerting a stronger inhibitory effect. In conclusion, HYP increases the radiosensitivity of esophageal carcinoma cells, offering considerable promise for application in the clinical treatment of EC.

This review examines hormone replacement therapy (HRT) in cases of surgical menopause following gynecological malignancies. It aims to capture current knowledge, summarize recent findings, and provide recommendations for clinical settings. Unlike natural menopause, surgical menopause occurs abruptly, without an adjustment period, and is associated with a notably higher risk of fractures, arthritis, cognitive decline, dementia, Parkinson's disease, and various metabolic disorders affecting glucose and lipid levels-all of which contribute to an increased risk of major cardiovascular events. In 2017, The North American Menopause Society recommended that, barring contraindications, HRT should be initiated in women who enter surgical menopause before age 45. If these women do not experience vasomotor symptoms or other issues, HRT should be maintained consistently at least until age 52. This guideline reflects contemporary knowledge and is the result of a multidisciplinary consensus, based on a review of existing literature and several randomized clinical trials focusing on women who have survived gynecological cancers and whose quality of life is significantly impacted by surgical or early menopause. Estrogen supplementation is particularly beneficial, as it is linked to marked improvements in quality of life, including delayed onset of chronic cardiovascular issues, reduced fracture risk, enhanced cognitive function, reduced inflammation, and improved self-esteem, as well as better social and work performance. Clinical implementation of HRT, however, requires a highly individualized approach. This approach must consider the type and stage of malignancy, histopathological characteristics, risk factors for recurrence (such as diet, concurrent medications, medical history, and genetic predispositions), and a thorough assessment of the potential benefits and risks of HRT, as well as the patient's personal wishes and expectations.

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.