摘要：
Introduction Glucosylceramidase beta 1 (GBA1) mutations are a genetic risk factor for Parkinson's disease (PD), though most carriers do not develop the disease. This study aimed to identify exposure factors linked to PD in GBA1 carriers and assess clinical features and the probability of prodromal PD in non-manifesting carriers.
Glucosylceramidase beta 1 (GBA1) mutations are a genetic risk factor for Parkinson's disease (PD), though most carriers do not develop the disease. This study aimed to identify exposure factors linked to PD in GBA1 carriers and assess clinical features and the probability of prodromal PD in non-manifesting carriers.
Methods Data from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China was used, including 59 GBA1 non-manifesting carriers, 62 controls, and 107 GBA1-associated PD, of whom 81 were in the early stage. Exposure factors included pesticide/solvent exposure, smoking, alcohol, and tea consumption. Logistic regression assessed the association between exposure factors and PD. Clinical characteristics were evaluated using multiple scales, relevant markers were collected based on the Movement Disorders Society criteria. A naive Bayesian classifier method determined the probability of prodromal PD in GBA1 non-manifesting carriers and controls.
Data from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China was used, including 59 GBA1 non-manifesting carriers, 62 controls, and 107 GBA1-associated PD, of whom 81 were in the early stage. Exposure factors included pesticide/solvent exposure, smoking, alcohol, and tea consumption. Logistic regression assessed the association between exposure factors and PD. Clinical characteristics were evaluated using multiple scales, relevant markers were collected based on the Movement Disorders Society criteria. A naive Bayesian classifier method determined the probability of prodromal PD in GBA1 non-manifesting carriers and controls.
Results After adjusting for sociodemographic variables, pesticide/solvent exposure was positively associated with PD in GBA1 carriers (OR 8.40; 95 % CI 2.50–28.20), while smoking was inversely associated with PD (OR 0.18; 95 % CI 0.05–0.62). Rapid eye movement sleep behavior disorder, constipation, hyposmia, and cognitive deficits were more severe in early-stage GBA1-associated PD than in carriers and controls. Clinical symptoms and the probability of prodromal PD were similar between carriers and controls.
After adjusting for sociodemographic variables, pesticide/solvent exposure was positively associated with PD in GBA1 carriers (OR 8.40; 95 % CI 2.50–28.20), while smoking was inversely associated with PD (OR 0.18; 95 % CI 0.05–0.62). Rapid eye movement sleep behavior disorder, constipation, hyposmia, and cognitive deficits were more severe in early-stage GBA1-associated PD than in carriers and controls. Clinical symptoms and the probability of prodromal PD were similar between carriers and controls.
Conclusions PD in GBA1 carriers is closely linked to exposure factors. Early-stage GBA1-associated PD shows significant prodromal symptoms, which are not evident in carriers. The probability of prodromal PD in carriers is similar to that in controls.
PD in GBA1 carriers is closely linked to exposure factors. Early-stage GBA1-associated PD shows significant prodromal symptoms, which are not evident in carriers. The probability of prodromal PD in carriers is similar to that in controls.
摘要：
BACKGROUND: Neuronal senescence is a common pathological feature of various neurodegenerative diseases, with ferroptosis playing a significant role. This study aims to investigate the role of ErbB4 receptor activation in preventing D-Galactose (D-gal)-induced neuronal senescence. METHODS: Mice subjected to D-gal-induced aging were administered a small molecule ErbB4 receptor agonist (E4A), identified via virtual screening, melatonin, or a combination of both. Behavioral assessments were conducted to evaluate therapeutic efficacy in memory and cognitive functions. Immunofluorescence staining, western blot, and biochemical assays were primarily employed to assess changes in both senescence- and ferroptosis-related molecules in mouse hippocampal tissues in response to each treatment. Additionally, mouse hippocampal HT22 neuronal cell cultures were utilized to corroborate the in vivo findings. RESULTS: The targeted activation of ErbB4 receptor by E4A significantly ameliorated the behavioral deficits induced by D-gal in mice, demonstrating an effect comparable to that of melatonin, a natural inhibitor of in vivo senescence and ferroptosis. Both E4A and melatonin mitigated D-gal-induced aging in hippocampal neurons of mice. This was evidenced by the upregulation of Lamin B1 and the downregulation of P53, P21, P16, GFAP, and Iba-1 expression levels. Moreover, D-gal treatment markedly decreased the protein expression of the ferroptosis inhibitor Nrf2 while augmenting the expression of the ferroptosis promoter TFRC. These alterations were partially reversed by the individual administration of E4A and melatonin. In vitro studies further corroborated that D-gal treatment significantly and concurrently induced the expression of senescence markers and ferroptosis promoters. However, both E4A and melatonin were able to significantly reverse these changes. Additionally, E4A markedly ameliorated Erastin-induced ferroptosis in mouse hippocampal neuronal cells. CONLUSION: Our findings suggest that targeted activation of ErbB4 receptor may be a viable strategy for treating neuronal senescence by inhibiting ferroptosis, thereby offering a potential therapeutic avenue for senescence-associated neurodegenerative diseases.
摘要：
Sepsis-associated acute respiratory distress syndrome (ARDS) is a heterogeneous disease with high morbidity and mortality. Lactylation plays a crucial role in sepsis and sepsis-induced lung injury. This study aimed to identify distinct lactylation-based phenotypes in patients with sepsis-associated ARDS and determine relevant molecular biomarkers. We analyzed blood transcriptome and clinical data from patients with sepsis-associated ARDS and calculated the lactylation activity. KEGG pathway analysis, drug sensitivity prediction, and immune cell infiltration analysis were performed. Candidate molecular biomarkers were identified by intersecting the feature genes extracted from four machine learning models. Lactylation activity showed significant heterogeneity among patients with sepsis-associated ARDS, which enabled the classification into low- and high-lactylation activity phenotypes. Patients with high-lactylation experienced longer hospital stays and higher mortality rates, as well as distinct signaling pathways, drug responses, and circulating immune cell abundances. Six key markers (ALDOB, CCT5, EP300, PFKP, PPIA, and SIRT1) were identified to differentiate the two lactylation activity phenotypes, all significantly correlated with circulating immune cell populations. This study revealed significant heterogeneity in lactylation activity phenotypes among patients with sepsis-associated ARDS and identified potential biomarkers to facilitate the application of these phenotypes in clinical practice.
作者：
Luo, Sihuan;Zhao, Xiaomei;Wang, Yijin;Jiang, Miao;Cao, Yi
期刊：
Food and Chemical Toxicology,2025年197:115304 ISSN：0278-6915
通讯作者：
Cao, Y
作者机构：
[Zhao, Xiaomei; Wang, Yijin; Luo, Sihuan; Cao, Yi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Jiang, Miao] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Peoples R China.
通讯机构：
[Cao, Y ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
关键词：
Autophagy;In vivo toxicity;Lipid profiles;Nanoplastics;Oral exposure
摘要：
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
摘要：
SUMOylation, the covalent attachment of small ubiquitin-like modifier proteins (SUMO) to lysine residues of target substrates, has emerged as a crucial posttranslational modification regulating various cellular processes. Recent studies have revealed that SUMOylation also plays significant roles in host-pathogen interactions during bacterial infections. On the one hand, SUMOylation can modulate host innate immune responses, such as inflammatory signaling and autophagy, to defend against invading bacteria. On the other hand, certain bacterial pathogens have evolved strategies to exploit or manipulate the host SUMOylation machinery to promote their survival and replication. Some bacterial effector proteins directly target host SUMO enzymes or SUMO-conjugated substrates to disrupt host defense mechanisms.Interestingly, a few bacteria have been found to possess their own SUMOylation systems that may contribute to bacterial virulence and stress adaptation. This review summarizes the current understanding of the complex interplay between SUMOylation and bacterial infection, highlighting the dual roles of SUMOylation in host defense and bacterial pathogenesis. We discuss the mechanisms by which SUMOylation regulates host immune responses against bacterial infection and how bacterial pathogens hijack host SUMOylation for their own benefit. Moreover, we explore the potential of targeting SUMOylation as a novel therapeutic strategy for combating bacterial infections. Further research into the intricate relationship between SUMOylation and bacterial infection may provide valuable insights for developing innovative antiinfective therapies.
通讯机构：
[Tan, XF; Yang, QL ; Wu, GL] U;Univ South China, Affiliated Hosp 1, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
NIR-II;Phototheranostics;Endoplasmic reticulum;Triple-negative breast cancer;Intermolecular π–π stacking interaction
摘要：
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by an extremely poor prognosis. Photoimmunotherapy has emerged as a promising strategy for the treatment of TNBC. This approach works by selectively destroying tumor cells, releasing tumor-associated antigens, activating the immune system, and effectively inhibiting tumor proliferation and metastasis. However, the majority of current phototheranostic approaches are hindered by limited tissue penetration in the first near-infrared (NIR-I) and ultraviolet-visible (UV-Vis) regions. Additionally, due to the lack of specific subcellular targets, it may be difficult to effectively treat deep-seated lesions with ambiguous and extensive boundaries caused by TNBC metastases. Consequently, the development of effective, deep-penetrating, organelle-targeted phototheranostics is essential for enhancing treatment outcomes in TNBC. This work proposes a novel molecular design strategy of NIR-II phototheranostics to realize planar rigid conjugation and alkyl chain functionalization. The di-hexaalkyl chains in a vertical configuration on the donor (4H-cyclopenta[2,1-b:3,4-b'] dithiophene) and shielding units (fluorene) are introduced to construct a S-D-A-D-S type NIR-II phototheranostics (IR-FCD). The planar and rigid structure of IR-FCD exhibits a robust intramolecular charge transfer capability, a lower band gap, enhanced photon absorption properties, and significant steric hindrance from vertically arranged alkyl chains to minimize non-radiative energy loss. By incorporating N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide at the terminus of an elongated alkyl chain, followed by self-assembly into DSPE-S-S-PEG2000, NIR-II excitable phototheranostics (IR-FCD-Ts NPs) with endoplasmic reticulum (ER) targeting capability were successfully synthesized for imaging-guided photoimmunotherapy of TNBC. The IR-FCD-Ts NPs demonstrate exceptional optical characteristics, with maximum absorption at 1068nm (extending to 1300nm) and emission at 1273nm (extending to 1700nm), along with a high molar absorption coefficient of 2.76*10(4)L/mol·c at 1064nm in aqueous solution. Under exposure to 1064nm laser irradiation, IR-FCD-Ts NPs exhibit superior photothermal properties and have the potential for photodynamic therapy. By targeting ER, thereby inducing ER stress and significantly enhancing immunogenic cell death (ICD) in tumor cells, it triggers a strong antitumor immune response and inhibits the proliferation and metastasis of TNBC.
摘要：
Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
摘要：
Background: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a recently developed composite indicator of atherogenic lipids. Nevertheless, few studies concern the relationship between NHHR and early-onset post-stroke depression (PSD). Methods: After two weeks of acute ischemic stroke (AIS), early-onset PSD was identified. The Hamilton Depression Scale-17 items (HAMD-17) was used to assess the severity of depression. Patients with HAMD-17 scores ≥7 were divided into an early-onset PSD group. Spearman rank correlation analysis was employed to evaluate the associations between NHHR and HAMD scores across all patients. Logistic regression analysis was conducted to investigate the associations between the NHHR and early-onset PSD. Sensitivity analyses were performed to test the robustness of our findings. Receiver operating characteristic curve (ROC) analysis was used to determine the predictive value of the NHHR for early-onset PSD. Results: Among the 846 patients who were enrolled prospectively, a total of 283 (33.45%) patients were diagnosed with early-onset PSD. The NHHR showed a positive correlation with the HAMD-17 scores (r=0.498, P<0.001). A binary logistic regression model demonstrated that the NHHR (odds ratio [OR], 1.796; 95% confidence interval [CI] 1.452-1.996, P<0.001) was an independent factor for early-onset PSD. The NHHR for early-onset PSD had an area under the curve (AUC) value of 0.798. Conclusions: The findings suggest that the NHHR may be an independent risk factor for early-onset PSD, providing valuable insights for prevention and prognostic management in affected patients.
摘要：
Mycoplasma represents a unique genus of prokaryotic bacteria distinguished by the absence of a cell wall, a characteristic that sets it apart from other bacteria. Within the Mollicutes class, phylogenetic analysis reveals three distinct categories: Spiroplasma, Mycoplasma and Acholeplasma. Mycoplasmas within Pneumoniae are recognized for their capacity to induce a range of diseases in both humans and animals, frequently impacting respiratory and reproductive health. The representative strains in Pneumoniae group, particularly the M. pneumoniae clusters, have garnered significant attention due to their remarkable ability to adhere to, invade, and traverse host cells. This ability is facilitated by specialized structures known as attachment organelles, which possess a unique cytoskeletal structure that supports a distinctive gliding motility mechanism. This mode of motility is distinct from that observed in eukaryotes and the majority of bacteria. The gliding machinery of Mycoplasma is a complex assembly consisting of both surface and internal components, including a terminal button, paired plates, and a structure resembling a bowl or wheel. The internal architecture of the attachment organelles provides the essential scaffold for the operation of this sophisticated motility system. Mycoplasma's gliding motility is crucial for its infection process and its capacity to evade the host immune defenses. Understanding the role of this motility to immune evasion can offer profound insights into the pathogenesis of these bacteria, could pave the way for the development of more effective therapeutic strategies against diseases caused by Mycoplasma and related species.
摘要：
Acute kidney injury (AKI) is associated with poor prognosis. New biomarkers, like neutrophil gelatinase-associated lipocalin (NGAL), are helpful for early warning of AKI. This study aims to investigate the accuracy of NGAL in evaluating the perioperative AKI of liver transplantation. The four databases, PubMed, Web of Science, Embase, and Cochrane Library, were searched for relevant studies published from database inception to August 2023. Results were pooled using random-effects models, and heterogeneity was examined. A total of 16 case-control studies with 1271 patients were included. The results showed that both preoperative [standardized mean difference (SMD) = 0.53; 95% confidence interval (CI): 0.15, 0.91; P < 0.001] and postoperative NGAL levels (SMD = 0.63; 95% CI: 0.24, 1.03; P < 0.001) were higher in the AKI group compared with the non-AKI group. Subgroup analysis by continents showed higher preoperative NGAL levels in AKI patients in the European population (SMD = 1.63; 95% CI: 0.55, 0.27; P = 0.003), but no differences in Asian, African, North American, and South American. Subgroup analysis by continents revealed higher postoperative NGAL levels in the European (SMD = 1.63; 95% CI: 0.55, 0.27; P = 0.002) and Asian populations (SMD = 0.42; 95% CI: 0.04, 0.81; P = 0.039). Higher postoperative NGAL levels in plasma and urine were observed in AKI patients compared with non-AKI patients [plasma (SMD = 1.29; 95% CI: 0.21, 2.38; P = 0.011), urine (SMD = 0.88; 95% CI: 0.18, 1.59; P = 0.035)], while there was no difference in African, North American, South American, and serum NGAL. NGAL level may be an important biomarker for early detection of AKI in the perioperative period of liver transplantation.
摘要：
Outer membrane vesicles (OMVs) derived from Pseudomonas aeruginosa drive inflammation by metabolically reprogramming macrophages to favor aerobic glycolysis. This study shows that OMVs trigger this metabolic shift via Toll-like receptors 2 and 4 (TLR2/4)-dependent activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. OMV-stimulated macrophages exhibited increased glucose uptake, lactate production, and expression of key glycolytic enzymes, resulting in a higher extracellular acidification rate and a lower oxygen consumption rate. Inhibition of the PI3K/Akt pathway reversed these metabolic changes. Crucially, this metabolic reprogramming was required for OMV-induced secretion of pro-inflammatory cytokines, as inhibition of glycolysis via 2-deoxy-D-glucose treatment attenuated the inflammatory response both in vitro and in vivo. These findings reveal that P. aeruginosa OMVs control metabolism in macrophages through the TLR2/4-PI3K/Akt axis to promote a pro-inflammatory state and identifies glycolysis as a potential therapeutic target for bacteria-associated inflammatory diseases.
作者机构：
[Tian, Qingzhen; Tang, Zheng; Zhang, Ziyu; Niu, Xiangheng; Li, Shu] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Lin, YH; Du, Dan; Niu, Xiangheng; Lin, Yuehe] Washington State Univ, Sch Mech & Mat Engn, Pullman, WA 99164 USA.;[Zhang, Xiao] Washington State Univ, Sch Chem Engn & Bioengn, Pullman, WA 99164 USA.
通讯机构：
[Lin, YH ; Niu, XH] W;[Niu, XH ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Washington State Univ, Sch Mech & Mat Engn, Pullman, WA 99164 USA.
关键词：
biomarkers;biomedical applications;catalytic signal amplifications;disease diagnosis;nanozymes
摘要：
An overview of nanozyme‐enabled biomedical sensing and diagnosis is presented. The preparation of nanozymes is first summarized, followed by a discussion of typical strategies that are applied to promote the catalytic specificity and activity of nanozymes; whereafter, the main use of nanozymes in biomarker detection and disease diagnosis is discussed; finally, development trends are forecasted, and corresponding challenges are also pointed out. Abstract As nanoscale materials with the function of catalyzing substrates through enzymatic kinetics, nanozymes are regarded as potential alternatives to natural enzymes. Compared to protein‐based enzymes, nanozymes exhibit attractive characteristics of low preparation cost, robust activity, flexible performance adjustment, and versatile functionalization. These advantages endow them with wide use from biochemical sensing and environmental remediation to medical theranostics. Especially in biomedical diagnosis, the feature of catalytic signal amplification provided by nanozymes makes them function as emerging labels for the detection of biomarkers and diseases, with rapid developments observed in recent years. To provide a comprehensive overview of recent progress made in this dynamic field, here an overview of biomedical diagnosis enabled by nanozymes is provided. This review first summarizes the synthesis of nanozyme materials and then discusses the main strategies applied to enhance their catalytic activity and specificity. Subsequently, representative utilization of nanozymes combined with biological elements in disease diagnosis is reviewed, including the detection of biomarkers related to metabolic, cardiovascular, nervous, and digestive diseases as well as cancers. Finally, some development trends in nanozyme‐enabled biomedical diagnosis are highlighted, and corresponding challenges are also pointed out, aiming to inspire future efforts to further advance this promising field.
通讯机构：
[Zhang, ZM ] U;Univ South China, Peoples Hosp Chenzhou 1, Dept Anesthesiol, Affiliated ChenZhou Hosp,Hengyang Med Sch, Chenzhou 423000, Hunan, Peoples R China.
关键词：
cancer pain;dexmedetomidine;opioid-sparing;opioids;α-2 adrenergic receptors
摘要：
BACKGROUND AND OBJECTIVE: Cancer pain treatment faces challenges such as ineffective pain management, high-dose opioid use, and insufficient analgesia. Dexmedetomidine (DEX), a novel α2 receptor agonist, is a potential adjuvant analgesic. Its analgesic mechanism involves central coeruleus cell hyperpolarization, activation of peripheral, spinal cord, and spinal α2 receptors, and regulation of cellular signaling pathways and inflammatory factors. DEX reduces harmful neurotransmitter production and pain signal transmission and enhances opioid analgesia while decreasing opioid use and tolerance. This review introduces the main mechanisms of DEX and its potential for treating complex and refractory cancer pain. METHODS: We conducted literature searches using the terms "dexmedetomidine," "cancer pain," "opioid sparing," "analgesic mechanism," and their combinations in PubMed, Embase, Cochrane Library, and Web of Science. We systematically retrieved research articles, reviews, and editorials published in English up to mid-December 2024. All identified publications were reviewed, and their key references were cross-checked to ensure a comprehensive and high-quality review. KEY CONTENT AND FINDINGS: Preclinical and clinical studies have demonstrated the advantages and potential of DEX in cancer pain management. DEX has intrinsic analgesic properties and can significantly relieve cancer pain by interacting with opioids, thereby delaying the development of opioid tolerance. It is particularly suitable for patients with refractory cancer pain and provides effective treatment whether used as an analgesic or an anesthetic adjuvant. CONCLUSIONS: DEX is a promising adjuvant for cancer pain management, utilizing multi-mechanism analgesia and opioid-sparing effects to address unmet needs in refractory cases. Preclinical and clinical studies highlight efficacy heterogeneity across different cancer types and limited long-term safety data. High-quality, multicenter randomized controlled trials are needed to determine the optimal dose, refine dosing regimens, and verify results across diverse populations. Until further evidence is available, DEX should be considered a valuable adjunct in individualized, multimodal analgesic strategies, with careful monitoring of hemodynamic parameters and central nervous system adverse events.
作者机构：
[Li, Pian; He, Junyan; Yang, Dong] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Xiaoli] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.;[Tan, Yini; Li, Yi] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Obstet & Gynecol, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, Y ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Obstet & Gynecol, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Endometrial carcinoma;Estrogen receptor;Lymphovascular space invasion;Myometrial invasion;Progesterone receptor
摘要：
Background It is crucial to identify the high-risk factors associated with the recurrence and metastasis of endometrial cancer (EC) in order to implement more precise clinical stratification and management strategies for EC patients. Methods A total of 336 patients with stage I-III EC were retrospectively analyzed. According to the recurrence site, they were divided into locoregional recurrence (LR) and poor-prognosis recurrence (PPR). The factors that may affect the prognosis of EC were analyzed and the subgroups were analyzed. Results Among the no recurrence(NR), LR and PPR groups, 5-year OS were 89.4%, 60.2% and 46.8%, 5-year RFS were 100%, 15.4% and 6.4%. The FIGO stage, molecular classification, lymphovascular space invasion (LVSI) and smoking history were independent risk factors affecting 5-year OS and 5-year RFS in EC patients (p < 0.05). Pathological type and progesterone receptor (PR) were independent risk factors affecting 5-year OS (p < 0.05). Histologic Grade and adjuvant therapy were independent risk factors affecting 5-year RFS (p < 0.05). Myometrial invasion, LVSI and FIGO stage were independent risk factors in the LR subgroup (p < 0.05), FIGO stage, ER and PR were independent risk in the PPR subgroup (p < 0.05). Conclusions Patients with myometrial invasion ≥ 1/2 and substantial LVSI may be more likely to have LR, while patients with positive ER and PR are more likely to have PPR. We need to pay attention to these factors to help us judge the prognosis of EC patients.
摘要：
This study aimed to create a personalized risk assessment model for asymptomatic intracerebral hemorrhage (aICH) following endovascular thrombectomy (ET) to aid clinical decision-making.Between 2019 and 2023, 469 inpatients with acute ischemic stroke (AIS) who received ET treatment within 24h of onset were recruited from three centers. Patients were randomly assigned to either a training or validation cohort. Univariate and multivariate logistic regression analyses were conducted to identify independent factors for aICH. A nomogram-based model was developed for personalized risk assessment for aICH following ET. The model's usability was evaluated using the receiver operating characteristic (ROC) curve, and a calibration curve was plotted to compare predicted probabilities with actual occurrences. The feasibility of the model for practical clinical application was assessed using decision curve analysis.Four independent risk factors for aICH in patients with AIS following ET were identified: preoperative Alberta Stroke Program Early Computed Tomography score [odds ratio (OR) = 0.686, 95% confidence interval (CI): 0.581-0.811], time from onset to surgery completion (OR = 1.186, 95% CI: 1.097-1.282), intraoperative arterial thrombolysis (OR = 2.405, 95% CI: 1.289-4.487), and Careggi collateral score (OR = 0.560, 95% CI: 0.422-0.743). ROC analysis indicated that the model demonstrated excellent accuracy and discrimination with area under the curve values of 0.812 (95% CI: 0.763-0.861) and 0.896 (95% CI, 0.843-0.949) for the training and validation cohorts, respectively.This nomogram-based model is a reliable personalized tool for evaluating the risk of aICH in patients with AIS after ET.
期刊：
Molecular and Cellular Biochemistry,2025年480(4):2143-2157 ISSN：0300-8177
通讯作者：
Wang, J
作者机构：
[Jiang, Tingting] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Dept Clin Lab, Hengyang 421000, Peoples R China.;[Zeng, Qun] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421000, Peoples R China.;[Wang, Jing] Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Peoples R China.;[Wang, Jing] Changsha Med Univ, Hunan Prov Univ Key Lab Fundamental & Clin Res Fun, Changsha 410219, Peoples R China.;[Wang, Jing] Changsha Med Univ, Clin Coll 1, Changsha 410219, Peoples R China.
通讯机构：
[Wang, J ] C;Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Peoples R China.;Changsha Med Univ, Hunan Prov Univ Key Lab Fundamental & Clin Res Fun, Changsha 410219, Peoples R China.;Changsha Med Univ, Clin Coll 1, Changsha 410219, Peoples R China.
摘要：
FHL2 (Four-and-a-half LIM domain protein 2) is a crucial factor involved in cardiac morphogenesis, the process by which the heart develops its complex structure. It is expressed in various tissues during embryonic development, including the developing heart, and has been shown to play important roles in cell proliferation, differentiation, and migration. FHL2 interacts with multiple proteins to regulate cardiac development as a coactivator or a corepressor. It is involved in cardiac specification and determination of cell fate, cardiomyocyte growth, cardiac remodeling, myofibrillogenesis, and the regulation of HERG channels. Targeting FHL2 has therapeutic implications as it could improve cardiac function, control arrhythmias, alleviate heart failure, and maintain cardiac integrity in various pathological conditions. The identification of FHL2 as a signature gene in atrial fibrillation suggests its potential as a diagnostic marker and therapeutic target for this common arrhythmia.
作者机构：
[Yao, Xiang-Rong; He, Jun-Yan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Peoples R China.;[Yao, Xiang-Rong; Xiao, Fang-Zhu] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Xiao, Wen-Tao] Nantong Univ, Affiliated Hosp, Med Sch, Dept Radiat Oncol, Nantong, Peoples R China.;[Huang, Cui-Qin] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Pathol, Hengyang, Peoples R China.
通讯机构：
[He, JY ; Huang, CQ ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Peoples R China.;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Pathol, Hengyang, Peoples R China.
摘要：
Head and neck squamous cell carcinoma (HNSC) is a prevalent and aggressive malignancy with poor prognosis, underscoring the need for novel biomarkers and therapeutic strategies. This study investigates the role of C16orf74 as a potential diagnostic and prognostic biomarker in HNSC. Bioinformatics analyses revealed that C16orf74 is significantly overexpressed in HNSC and is associated with advanced disease stages, therapy resistance, and shorter overall and progression-free survival. A prognostic nomogram integrating C16orf74 expression with clinicopathological features demonstrated robust predictive performance. Functional enrichment and immune infiltration analyses suggest that high C16orf74 expression might contribute to an immunosuppressive tumor microenvironment by reducing key immune cell populations, such as B cells, T cells, and natural killer cells, which are critical for anti-tumor immunity. Moreover, C16orf74 expression was inversely associated with immune checkpoint expression and immunotherapy response, highlighting its potential as a predictive biomarker for immune checkpoint blockade (ICB) efficacy. Drug sensitivity analyses identified potential therapeutic agents, including arsenic trioxide, carmustine, vincristine, quercetin, and carboplatin for patients with high C16orf74 expression. These findings highlight the potential of C16orf74 as a biomarker and therapeutic target to improve HNSC management.
摘要：
N-acetyltransferase 10 (NAT10) is a key enzyme for N4-acetylcytidine (ac4C) modification of mRNA, but its functions in the central nervous system remain unclear. In this study, we explored the spatial localization of NAT10 and observed the alterations of it in the brain of l ipopolysaccharide (LPS) treated mice. Meanwhile, we observed the changes of depression-like behaviors after blocking NAT10 systematically with its inhibitor Remodelin or knockdown hippocampal NAT10 in LPS treated mice and explored its potential mechanism. After having showed the NAT10 is highly expressed in the mouse brain and mainly co-localized with the neuron, we found that LPS elicited hippocammpal NAT10 expression, and chronic administration of NAT10 inhibitor Remodelin, instead of acute administration, prevented LPS-induced depression-like behavior without affecting acute sickness behavior . Consistently, viral-mediated NAT10 knock-down in the hippocampus could also relieve depression-like behaviors in the mice challenged with LPS. And we identified that hippocampal microglia represented a cellular target of NAT10 inhibitor. The role of both pharmacological agents and viral tool in the block of NAT10 to alleviate depressive-like behavior suggests that NAT10 may be a valuable target for drug discovery in depression.
N-acetyltransferase 10 (NAT10) is a key enzyme for N4-acetylcytidine (ac4C) modification of mRNA, but its functions in the central nervous system remain unclear. In this study, we explored the spatial localization of NAT10 and observed the alterations of it in the brain of l ipopolysaccharide (LPS) treated mice. Meanwhile, we observed the changes of depression-like behaviors after blocking NAT10 systematically with its inhibitor Remodelin or knockdown hippocampal NAT10 in LPS treated mice and explored its potential mechanism. After having showed the NAT10 is highly expressed in the mouse brain and mainly co-localized with the neuron, we found that LPS elicited hippocammpal NAT10 expression, and chronic administration of NAT10 inhibitor Remodelin, instead of acute administration, prevented LPS-induced depression-like behavior without affecting acute sickness behavior . Consistently, viral-mediated NAT10 knock-down in the hippocampus could also relieve depression-like behaviors in the mice challenged with LPS. And we identified that hippocampal microglia represented a cellular target of NAT10 inhibitor. The role of both pharmacological agents and viral tool in the block of NAT10 to alleviate depressive-like behavior suggests that NAT10 may be a valuable target for drug discovery in depression.
