Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Aim To investigate the protective effect of ganglioside(GM1)on ischemic-hypoxic brain injury(HIBI)in neonatal rats and the related mechanism.Methods Eighty,7-day old SD neonatal rats were randomly divided into four groups:sham operated group(sham),HIBM group,GM1 group and GM1+PIM-1 inhibitor group(GM1+PIM-1 inhibitor),with 20 rats in each group.After successful construction of the HIBI model,the neonatal rats were injected intrap-eritoneally with GM1(20 mg·kg-1·d-1)for three days in the GM1 group.The neonatal rats were given intraperitoneal injection of GM1(20 mg·kg-1·d-1)after a one-time injection of PIM-1 inhibitor(5 mg·kg-1)into the lateral ventricle for three days in the GM1+PIM-1 inhibitor group.Sham and HIBI groups were injected intraperitoneally with equal amounts of saline.Longa method was uses to assess the neurologi-cal impairment;TTC staining was used to detect the volume ratio of cerebral infarction;HE staining was used to observe the hippocampal histopathology;TUNEL staining was used to detect the apoptosis of hippocampal neurons;ELISA was used to detect the levels of IL-1β and IL-18 in hippocampal tissues;Western blot was used to detect PIM-1/PI3K/Akt sig-naling pathway proteins and pyroptosis-related proteins(NLRP3,ASC,caspase-1 p20,GSDMD-N).Results Compared with the sham group,the Longa score,cere-bral infarct volume,hippocampal neuronal apoptosis rate,IL-1 β,IL-18 levels,and pyroptosis-related protein expression were significantly higher(P＜0.05),while PIM-1 protein expression,p-PI3K/PI3K,and p-Akt/Akt ratio were significantly lower(P＜0.05)in the HIBI group.Compared with the HIBI group,the Longa score,cerebral infarct volume ratio,hippocampal neuro-nal apoptosis rate,IL-1 β,IL-18 levels,and pyroptosis-related protein expression were significantly lower(P＜0.05),while PIM-1 protein expression,p-PI3K/PI3K,and p-Akt/Akt ratio were significantly higher(P＜0.05)in the GM1 group of neonatal rats.Compared with the GM1 group,the Longa score,cerebral infarct volume ratio,hippocampal neuronal apoptosis rate,IL-1 β,IL-18 levels,and pyroptosis-related protein expres-sion were significantly higher(P＜0.05),while PIM-1 protein expression,p-PI3K/PI3K,and p-Akt/Akt ratio were significantly lower(P＜0.05)in the GM1+PIM-1 inhibitor group of neonatal rats.Conclusion GM1 ameliorates HIBI in neonatal rats by a mechanism related to activation of the PIM-1/PI3K/Akt signaling pathway and inhibition of hippocampal neuronal pyrop-tosis.

Aim To investigate the protective effect of ganglioside(GM1)on ischemic-hypoxic brain injury(HIBI)in neonatal rats and the related mechanism.Methods Eighty,7-day old SD neonatal rats were randomly divided into four groups:sham operated group(sham),HIBM group,GM1 group and GM1+PIM-1 inhibitor group(GM1+PIM-1 inhibitor),with 20 rats in each group.After successful construction of the HIBI model,the neonatal rats were injected intrap-eritoneally with GM1(20 mg·kg-1·d-1)for three days in the GM1 group.The neonatal rats were given intraperitoneal injection of GM1(20 mg·kg-1·d-1)after a one-time injection of PIM-1 inhibitor(5 mg·kg-1)into the lateral ventricle for three days in the GM1+PIM-1 inhibitor group.Sham and HIBI groups were injected intraperitoneally with equal amounts of saline.Longa method was uses to assess the neurologi-cal impairment;TTC staining was used to detect the volume ratio of cerebral infarction;HE staining was used to observe the hippocampal histopathology;TUNEL staining was used to detect the apoptosis of hippocampal neurons;ELISA was used to detect the levels of IL-1β and IL-18 in hippocampal tissues;Western blot was used to detect PIM-1/PI3K/Akt sig-naling pathway proteins and pyroptosis-related proteins(NLRP3,ASC,caspase-1 p20,GSDMD-N).Results Compared with the sham group,the Longa score,cere-bral infarct volume,hippocampal neuronal apoptosis rate,IL-1 β,IL-18 levels,and pyroptosis-related protein expression were significantly higher(P＜0.05),while PIM-1 protein expression,p-PI3K/PI3K,and p-Akt/Akt ratio were significantly lower(P＜0.05)in the HIBI group.Compared with the HIBI group,the Longa score,cerebral infarct volume ratio,hippocampal neuro-nal apoptosis rate,IL-1 β,IL-18 levels,and pyroptosis-related protein expression were significantly lower(P＜0.05),while PIM-1 protein expression,p-PI3K/PI3K,and p-Akt/Akt ratio were significantly higher(P＜0.05)in the GM1 group of neonatal rats.Compared with the GM1 group,the Longa score,cerebral infarct volume ratio,hippocampal neuronal apoptosis rate,IL-1 β,IL-18 levels,and pyroptosis-related protein expres-sion were significantly higher(P＜0.05),while PIM-1 protein expression,p-PI3K/PI3K,and p-Akt/Akt ratio were significantly lower(P＜0.05)in the GM1+PIM-1 inhibitor group of neonatal rats.Conclusion GM1 ameliorates HIBI in neonatal rats by a mechanism related to activation of the PIM-1/PI3K/Akt signaling pathway and inhibition of hippocampal neuronal pyrop-tosis.

OBJECTIVE: To explore the mechanism of crocin, a major active component of Crocus sativus (Zanghonghua), in regulating amyloid beta (Aβ) generation, endoplasmic reticulum (ER) stress, and autophagy in neuronal cells, with potential therapeutic applications in Alzheimer's disease (AD). METHODS: Mouse neuroblastoma Neuron2a (N2a) cells stably transfected with the human amyloid precursor protein (APP) Swedish mutant was used as a cellular model for AD (N2a/APP). Control cells were vector transfected (N2a/vector). The effects of 3 different doses of crocin on reactive oxygen species (ROS) generation, cytosolic calcium, and apoptosis were evaluated by flow cytometry. Aβ levels were determined by enzyme-linked immunosorbent assay. APP processing and ER stress proteins expressions were determined by Western blot. Autophagosome formation was evaluated by autophagy detection kit and confocal microscope. RESULTS: Crocin inhibited APP expression in N2a/APP cells and promoted α-cleavage of APP processing, while modestly reduced beta-secretase 1 (BACE1) and presenilin 1 (PS1, P<0.05 or P<0.01). ER stress markers, including the binding immunoglobulin protein/78-kD glucose-regulated protein (Bip/GRP78) and C/EBP homologous protein (CHOP), were elevated in N2a/APP cells compared to N2a/vector cells (P<0.05). Crocin could effectively reduce the levels of ER stress (P<0.05 or P<0.01). In addition, crocin enhanced autophagy by promoting formation of autophagosome (P<0.05 or P<0.01). CONCLUSION Crocin significantly inhibited Aβ generation by promoting α-cleavage of APP processing, inhibiting ER stress-associated unfolded protein response, and regulating autophagy.
Endoplasmic Reticulum Stress/drug effects* ; Autophagy/drug effects* ; Animals ; Endoplasmic Reticulum Chaperone BiP ; Mice ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Carotenoids/pharmacology* ; Humans ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Calcium/metabolism*

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.