Biomolecules & biomedicine最新文献

{"title":"Thymoquinone and 3HQ synergy inhibits CTX-M-15 ESBL.","authors":"Karem Ibrahem, Mohammad Alrabia, Asif Fatani, Sameer E M Alharthi, Hani Zakareya Asfour, Nabil A Alhakamy, Hatoon A Niyazi, Hisham N Altayb, Ahmad M Sait, Philip J R Day, Abdalbagi Alfadil","doi":"10.17305/bb.2025.12431","DOIUrl":"https://doi.org/10.17305/bb.2025.12431","url":null,"abstract":"<p><p>Bacterial infections remain a significant cause of mortality worldwide, further aggravated by the escalating issue of antibiotic resistance. Extended-Spectrum Beta-Lactamases (ESBLs) pose a substantial challenge, capable of hydrolyzing various beta-lactam antibiotics. The slow pace of drug discovery, coupled with the rapid emergence of drug-resistant bacteria, underscores the urgent need for innovative therapeutic solutions. Thymoquinone (TQ), derived from the seeds of Nigella sativa, has demonstrated notable antibacterial activity against Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa. Previous research has established the efficacy of quinoxaline derivatives, such as 3-hydrazinoquinoxaline-2-thiol (3HQ), against Methicillin-Resistant Staphylococcus aureus (MRSA). This study investigates the potential synergy between 3HQ and TQ against various clinical strains of ESBL. The minimum inhibitory concentrations (MICs) of TQ and 3HQ were evaluated against 18 clinical ESBL strains, revealing MIC values ranging from 16 to 128 µg/mL for both compounds. Furthermore, the interaction between TQ and 3HQ was assessed using a checkerboard assay, which demonstrated a 100% synergistic interaction, with a fractional inhibitory concentration index (FICI) of less than 0.5 against the ESBL strains. Docking and molecular dynamics simulations indicated that TQ exhibits a strong binding affinity and interaction profile comparable to that of RPX-7063. In contrast, 3-hydrazinoquinoxaline-2-thiol targets a different active site, potentially enhancing thymoquinone's binding efficiency. Collectively, these compounds may effectively inhibit CTX-M-15, as evidenced by their docking scores and interaction profiles. Further investigations, including in vivo studies, are essential to validate these findings. This research suggests a promising strategy for developing more effective treatments for ESBL infections, emphasizing the need for in vivo validation.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor glucose reprogramming suppresses cuproptosis: A review.","authors":"Xiao-Hang Song, Yi-Hang Ding, Jing-Song Chen","doi":"10.17305/bb.2025.12751","DOIUrl":"10.17305/bb.2025.12751","url":null,"abstract":"<p><p>Cuproptosis is a copper-dependent form of regulated cell death that begins when ferredoxin 1 (FDX1) reduces Cu²⁺ to Cu¹⁺, allowing the ion to bind lipoylated enzymes of the tricarboxylic-acid (TCA) cycle, drive protein aggregation, dismantle iron-sulphur clusters and trigger fatal proteotoxic stress. Most tumours, despite accumulating copper, evade this fate through glucose-metabolic rewiring. First, oncogenic stabilisation of hypoxia-inducible factor-1 alpha (HIF-1α) and MYC increases pyruvate dehydrogenase kinase (PDK) activity, which phosphorylates and inactivates the pyruvate dehydrogenase complex (PDC), shrinking the lipoylated target pool in mitochondria and cutting the feed into the TCA cycle. Second, glycolytic signalling suppresses cuproptosis-promoting genes such as FDX1 and dihydrolipoamide S-acetyltransferase while inducing the negative regulator glutaminase (GLS), further lowering copper sensitivity. Third, diversion of glycolytic intermediates into the pentose-phosphate pathway (PPP) supplies abundant nicotinamide adenine dinucleotide phosphate (NADPH), whereas enhanced glutamine catabolism furnishes glutamate; together these fuels expand reduced glutathione (GSH) and metallothionein (MT) pools that chelate Cu¹⁺ and quench reactive oxygen species exactly where cuproptosis is executed. Consequently, glycolysis-dependent cancer cells are far less sensitive to copper-ionophore drugs such as elesclomol or disulfiram than respiration-dependent counterparts, and clinical datasets consistently link high PDK and low PDC-subunit expression with poor prognosis. These insights highlight rational combination strategies: re-activating the TCA cycle with PDK inhibitors, draining PPP- or GLS-driven NADPH/GSH supply, and concurrently delivering copper ionophores could reopen the cuproptotic trap in tumours. Validating such approaches in vivo, charting upstream regulators of FDX1 and mapping crosstalk between cuproptosis and other lethal programmes remain key steps toward exploiting this copper-centred vulnerability in cancer therapy.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"251-261"},"PeriodicalIF":0.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the mechanism of Wnt/β-catenin pathway mediated by pterostilbene to reduce cerebral ischemia-reperfusion injury.","authors":"Yang Jin, Chunwang Fu, Ming Guo, Qiang Yang","doi":"10.17305/bb.2025.11743","DOIUrl":"10.17305/bb.2025.11743","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion injury (CIRI) is the primary cause of damage following ischemic stroke, with ferroptosis serving as a key pathophysiological factor in CIRI. Pterostilbene (PTE) has been shown to reduce cerebral ischemic injury, but whether its mechanism of action involves ferroptosis remains unclear. In this study, an in vitro model of mouse hippocampal neuron (HT22) cell injury and an in vivo mouse CIRI model were established. Treatments included PTE, the ferroptosis activator Erastin, and the Wnt signaling pathway inhibitor (Dkk-1). Cell damage was assessed using flow cytometry, MTT assay, lactate dehydrogenase (LDH) release assay, and Calcein-AM/PI staining. Oxidative stress and ferroptosis in cells and tissues were evaluated using biochemical kits and fluorescence staining. Additionally, histopathological staining was performed to assess brain tissue damage, while qRT-PCR and Western blot analyses were used to measure ferroptosis-related factors and Wnt/β-catenin pathway-related proteins in both cells and tissues. HT22 cells subjected to injury exhibited decreased viability and increased cell death (P < 0.05). Similarly, CIRI mice demonstrated pronounced cerebral infarction and neuronal damage. Ferroptosis, characterized by elevated levels of iron ions, lipid peroxides (ROS and MDA), and reduced antioxidant enzymes (GSH and GPX4), was significantly increased in both cells and tissues (P < 0.05). Correspondingly, ferroptosis-related protein levels were elevated (P < 0.05), while Wnt/β-catenin pathway-related protein levels were significantly decreased (P < 0.05). Treatment with Erastin and Dkk-1 exacerbated neuronal damage, intensified ferroptosis, and inhibited the Wnt/β-catenin pathway. Conversely, PTE treatment activated the Wnt/β-catenin pathway, reduced ferroptosis, and improved neuronal damage. Specifically, PTE upregulated the Wnt/β-catenin pathway, decreased peroxide accumulation, and antagonized ferroptosis, ultimately mitigating CIRI. These findings suggest that PTE protects against CIRI by modulating the Wnt/β-catenin pathway and alleviating ferroptosis-induced damage.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"2035-2049"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal microbiota transplantation alleviates radiation enteritis by modulating gut microbiota and metabolite profiles.","authors":"Qin Ding, Jing Xue, Nan Li, Zhihui Hu, Jianbo Song","doi":"10.17305/bb.2025.11835","DOIUrl":"10.17305/bb.2025.11835","url":null,"abstract":"<p><p>This study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"1992-2003"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular aspects of Angelman Syndrome: Defining the new path forward.","authors":"Jacqueline Fátima Martins de Almeida, Ilaria Tonazzini, Simona Daniele","doi":"10.17305/bb.2025.11724","DOIUrl":"10.17305/bb.2025.11724","url":null,"abstract":"<p><p>As a rare neuro-genetic disease, Angelman syndrome (AS) affects about 15 to 500 thousand people worldwide. The AS is an imprinting genomic disease characterized by the loss of function of the maternal UBE3A gene, located in the 15q11-q13. This gene encodes a ~100 kDa protein, the Ubiquitin-protein ligase E3A (UBE3A), that participates in the ubiquitination process, one of the post-translational protein modifications. In the brain, under normal conditions, the paternal allele of the UBE3A gene is silenced, with only the maternal allele being active. However, in individuals with AS, the maternal loss of function of this gene leads to the complete absence of UBE3A expression, resulting in multiple pathological features. Clinically, children diagnosed with AS exhibit a characteristic behavioral phenotype, including a happy demeanor, frequent and unmotivated laughter, movement, speech impairment, severe intellectual disability, and sleep problems. Since its discovery in 1965, significant progress has been made in understanding the genetic and pathophysiological aspects of AS. However, despite these advances, the molecular mechanisms underlying the disease remain incompletely understood, and no effective treatment currently exists. Current therapies focus solely on symptom management, and no approach has yet succeeded in reactivating the silenced paternal UBE3A allele. Therefore, this review highlights the epigenetic aspects involved in the AS in order to provide a better understanding and clarification of the mechanisms, hopefully paving the way for future research to improve the treatment of affected individuals.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"1928-1936"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>DPP4</i> rs17574 polymorphism and elevated DPP4 levels linked to fatty liver in subclinical atherosclerosis: GEA study findings.","authors":"Gilberto Vargas-Alarcón, Juan Reyes-Barrera, Guillermo Cardoso-Saldaña, Neftali Antonio-Villa, Giovanny Fuentevilla-Álvarez, José Manuel Fragoso, Rosalinda Posadas-Sánchez","doi":"10.17305/bb.2025.11950","DOIUrl":"10.17305/bb.2025.11950","url":null,"abstract":"<p><p>Dipeptidyl peptidase-4 (DPP4) concentrations are known to correlate with nonalcoholic fatty liver (FL), which is also associated with subclinical atherosclerosis (SA). This study aimed to determine whether DPP4 concentrations and the DPP4 rs17574 polymorphism are associated with FL in individuals with SA. The study included 378 participants with SA, of whom 143 had FL and 235 did not. DPP4 serum concentrations were measured using a Bioplex system, and DPP4 rs17574 genotypes were determined using TaqMan assays. Logistic regression was used to assess the relationships between FL, DPP4 concentrations, and rs17574 genotypes. Overall, DPP4 concentrations did not differ significantly between individuals with and without FL. No significant differences in DPP4 levels were observed among DPP4 genotypes in the total sample. However, within the FL group, significant differences in DPP4 concentration were observed across genotypes: AA genotype (134 [106-175] ng/mL), AG genotype (128 [114-149] ng/mL), and GG genotype (80 [71-117] ng/mL); P = 0.019. The DPP4 rs17574 polymorphism was associated with FL under a recessive model (P = 0.037). DPP4 concentration was also significantly associated with FL: the likelihood of presenting with FL increased by 6.2% for every 10 ng/mL increase in DPP4 levels (P = 0.009). These findings suggest that DPP4 concentration may serve as a biochemical risk marker for FL in individuals with SA. Moreover, the rs17574 polymorphism may influence DPP4 protein levels, particularly in those with FL. To our knowledge, this is the first study to describe an association between DPP4 concentration, the rs17574 polymorphism, and FL. Assessing DPP4 levels may offer a novel and effective strategy for risk stratification of FL in SA populations.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"2139-2147"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing ICU mortality prediction in community-acquired pneumonia: Combining fibrinogen-to-albumin ratio, CT severity score, PSI, and CURB-65.","authors":"Ece Unal Cetin, Ozge Kurtkulagi, Fatih Kamis, Murat Das, Esen Simsek, Adil Ugur Cetin, Yavuz Beyazit","doi":"10.17305/bb.2025.12127","DOIUrl":"10.17305/bb.2025.12127","url":null,"abstract":"<p><p>Community-acquired pneumonia (CAP) is a leading cause of ICU admissions, with significant morbidity and mortality. Traditional risk stratification tools, such as CURB-65, the pneumonia severity index (PSI), and computed tomography severity scores (CT-SS) are widely used for prognosis but could be improved by incorporating novel biomarkers. This retrospective study evaluated the fibrinogen-to-albumin ratio (FAR) as an additional predictor of 30-day mortality in ICU patients with CAP. A total of 158 CAP patients admitted to a tertiary care ICU were included. Baseline data encompassed demographic, clinical, laboratory, and radiological parameters, including FAR, CURB-65, PSI, and CT-SS. Logistic regression and receiver operating characteristic curve (ROC) analyses were conducted to assess mortality predictors. The 30-day mortality rate was 70.88% (112/158). Higher FAR, PSI, CURB-65, CT-SS, and lactate levels were independently associated with increased mortality (P < 0.05). FAR demonstrated strong discriminatory power (area under the receiver operating characteristic [AUROC]: 0.704) and significantly improved the predictive accuracy of established models. Adding FAR to PSI increased the AUROC from 0.705 to 0.791 (P = 0.009), while combining FAR, CT-SS, and PSI yielded the highest predictive accuracy (AUROC: 0.844, P = 0.032). These findings suggest that FAR, which reflects both inflammation and nutritional status, complements traditional risk assessment tools by providing a dynamic perspective. Integrating FAR into existing models enhances the identification of high-risk patients, enabling timely interventions and more efficient resource allocation in the ICU.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"2083-2091"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory role of exercise in heart failure and myocardial energy metabolism: A review.","authors":"Yuanhao Li, Dongli Gao, Peixia Li, Xulei Duan, Youli Liu, Chengyan Wu, Libo Wang, Xuehui Wang","doi":"10.17305/bb.2025.12072","DOIUrl":"10.17305/bb.2025.12072","url":null,"abstract":"<p><p>Myocardial energy metabolism is crucial for maintaining optimal heart function. The heart, having limited energy storage capacity, is dependent on a continuous energy supply; any disruptions or alterations in energy metabolism pathways can lead to insufficient myocardial energy, potentially triggering heart failure (HF). Exercise, as a safe and economical non-pharmacological intervention, is widely recognized to enhance cardiovascular health and modify myocardial energy metabolism patterns. However, the specific mechanisms by which exercise regulates myocardial metabolism to prevent and treat HF remain unclear. This review aims to detail the characteristics of myocardial metabolism under normal physiological and HF conditions, to further explore the impact of different exercise modalities on myocardial metabolism, and to summarize the molecular mechanisms by which exercise protects the heart by optimizing myocardial energy metabolism. Ultimately, this article aims to provide an in-depth understanding and evidence for the application of exercise interventions in cardiac rehabilitation.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"1898-1918"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX-9 as a prognostic marker in gastric adenocarcinoma.","authors":"Efe Yetişgin, Aysun Gökçe, Kutsal Doğan","doi":"10.17305/bb.2024.11928","DOIUrl":"10.17305/bb.2024.11928","url":null,"abstract":"<p><p>SRY-box transcription factor 9 (SOX9) has been reported to be overexpressed in a wide variety of gastrointestinal malignancies. While its role has been studied in gastric cancer (GC), the results remain conflicting. This study aimed to evaluate the relationship between SOX9 immunohistochemistry results and the pathological and clinical characteristics of gastric adenocarcinoma, assessing its potential as a prognostic marker. Gastric tissue samples from 150 patients with gastric cancer were included in the study. Tissue sections were stained using an anti-SOX9 antibody, and relevant data were retrospectively collected from digital records. Immunostaining results were scored based on the proportion and intensity of stained nuclei throughout the tumor. A final immunostaining score was calculated by multiplying the SOX9 intensity score by the proportion score. Strong SOX9 nuclear staining was observed in 68 patients (45.3%), while moderate staining was seen in 60 patients (40%). SOX9 nuclear staining was absent in three patients (2%). A final SOX9 immunostaining score of ≥10, classified as high expression, was identified in 60 patients (40%). Patients with higher SOX9 expression or strong intensity scores exhibited significantly larger tumor sizes, higher rates of perineural and vascular invasion, more advanced T or lymph node staging, and greater likelihoods of lymphatic or distant metastases compared to those with lower SOX9 expression or intensity scores (all P < 0.05). These findings suggest that SOX9 staining intensity and expression are associated with increased tumor malignancy and disease progression. Therefore, SOX9 may serve as a prognostic pathological indicator in GC patients.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"1982-1991"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant immunochemotherapy for resectable esophageal cancer: A study on efficacy and safety.","authors":"Xiaomin Wang, Bingxu Li, Zhiyong Zheng, Weijie Wang","doi":"10.17305/bb.2025.11806","DOIUrl":"10.17305/bb.2025.11806","url":null,"abstract":"<p><p>The combination of immunosuppressants and chemotherapy has reshaped the treatment landscape for esophageal cancer (EC). This study aimed to evaluate the effectiveness and safety of a neoadjuvant immunochemotherapy (nICT) regimen in patients with resectable EC. A total of 99 eligible patients were included. Data on patient characteristics, nICT regimens, surgical approaches, postoperative outcomes, adverse events (AEs) related to neoadjuvant therapy and surgery, overall survival (OS), and disease-free survival (DFS) were collected. OS, DFS, and safety were the primary endpoints. Cox regression analysis was used to identify prognostic factors in the overall population. Additionally, exploratory research was conducted to assess the clinical value of blood immune indicators in predicting tumor regression. Following surgery, 99.0% of patients achieved complete resection (R0). After neoadjuvant therapy, the number of patients with stage T0N0 increased, with complete or moderate responses being the most common outcomes according to American Joint Committee on Cancer (AJCC)/ College of American Pathologists (CAP)-tumor regression grading (TRG) evaluations (64.7%). The one-year OS and DFS rates were 91.6% and 49.3%, respectively. Grade ≥3 AEs related to neoadjuvant therapy occurred in 21.2% of patients, with gastrointestinal reactions being the most frequent (16 cases, 16.2%). No treatment-related deaths were reported. Grade ≥3 surgery-related AEs occurred in 10.1% of patients, with anastomotic leakage being the most common (six cases, 6.1%). Several factors were associated with significantly improved OS, including chemotherapy regimens combining paclitaxel with platinum, surgical approaches using laparoscopy or thoracotomy (left or right), an interval of ≤34 days between the last treatment and surgery, and the absence of positive lymph node detection. Higher cT staging was significantly associated with worse DFS. Blood immune markers, such as the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were found to predict tumor regression in EC patients. In summary, nICT demonstrated favorable effectiveness and safety in resectable EC. The choice of platinum-based chemotherapy agents, rather than the type of immunosuppressant, was associated with prognosis. Moreover, a shorter interval (≤34 days) between the final nICT administration and surgery was linked to improved outcomes.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"2127-2138"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}