1.Self-face Advantage Processing and Its Mechanisms
Xiao-Xia TANG ; Shu-Jia ZHANG ; Ying ZHANG ; Li WANG
Progress in Biochemistry and Biophysics 2025;52(7):1771-1791
Self-face is a unique and highly distinctive stimulus, not shared with others, and serves as a reliable marker of self-awareness. Compared to other faces, self-face processing exhibits several advantages, including the self-face recognition advantage, self-face attention advantage, and self-face positive processing advantage. The self-face recognition advantage manifests as faster and more accurate identification across different orientations and spatial frequency components, supported by enhanced early event-related potential (ERP) components, such as N170. Attentional biases toward self-face are evident in target detection during spatial tasks and the attentional blink effect in temporal paradigms. However, measurement sensitivity, perceptual load, and task demands contribute to some mixed findings. Positive biases further characterize the self-face processing advantage, with individuals perceiving their faces as more attractive or trustworthy than objective representations. These biases even extend to self-similar others, influencing social behaviors such as trust and voting preferences. Self-face processing advantages have been observed at an unconscious level and are regulated by several factors, including self-esteem, cultural differences, and multisensory integration. Cultural and individual differences play a crucial role in shaping self-face advantages. Individuals from Western cultures, which emphasize independent self-construal, exhibit stronger self-face biases compared to those from East Asian collectivist contexts. Self-esteem also modulates self-face advantages: high-self-esteem individuals generally maintain their self-face recognition advantage despite interference, exhibit attentional prioritization of self-faces, and demonstrate enhanced positive associations with subliminal self-faces. In contrast, low-self-esteem individuals display recognition vulnerabilities to social cues, show context-dependent attentional divergence (prioritizing others’ faces in task-oriented settings while prioritizing self-face in free-viewing tasks), and exhibit reversed positive associations with subliminal self-faces. Multisensory integration, such as synchronized visual-tactile cues, enhances self-face advantages and induces perceptual plasticity. This phenomenon is exemplified by the enfacement illusion, in which synchronous visual and tactile inputs update the mental representation of the self-face, leading to assimilation with another face. Neuroanatomically, self-face processing is predominantly lateralized to the right hemisphere and involves a network of brain regions, including the occipital lobe, temporal lobe, frontal lobe, insula, and cingulate gyrus. Disruptions in these networks are linked to self-face processing deficits in socio-cognitive disorders. For instance, autism spectrum disorder (ASD) and schizophrenia are associated with attenuated self-face advantages and abnormal neural activity in regions such as the right inferior frontal gyrus, insula, and posterior cingulate cortex. These findings suggest that self-face processing could serve as a potential biomarker for the early diagnosis and intervention of such disorders. In recent years, researchers have proposed various theoretical explanations for self-face processing and its advantage effects. However, some studies have reported no significant behavioral or neural advantages of self-faces over familiar faces, leaving the specificity of self-face a subject of debate. Further elucidation of self-face specificity requires the adoption of a face association paradigm, which controls for facial familiarity and helps determine whether qualitative differences exist between self-faces and familiar faces. Given the close relationship between self-face processing advantages and socio-cognitive disorders (e.g., ASD, schizophrenia), a deeper understanding of self-face specificity has the potential to provide critical insights into the early identification, classification, and intervention of these disorders. This research holds both theoretical significance and substantial social value.
2.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
;
Male
;
Rats
;
Nucleus Accumbens/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Depression/complications*
;
Membrane Glycoproteins/genetics*
;
Rats, Sprague-Dawley
;
Sleep Initiation and Maintenance Disorders/complications*
;
Neurons/metabolism*
;
Receptors, Immunologic/genetics*
;
Signal Transduction/drug effects*
;
Synapses/metabolism*
3.Clinical Characteristics and Prognostic Analysis of Newly Diagnosed Acute Myeloid Leukemia Patients with NRAS and KRAS Gene Mutations.
Zhang-Yu YU ; Bo CAI ; Yi WANG ; Yang-Yang LEI ; Bing-Xia LI ; Yu-Fang LI ; Yan-Ping SHI ; Jia-Xin CHEN ; Shu-Hong LIU ; Chang-Lin YU ; Mei GUO
Journal of Experimental Hematology 2025;33(3):682-690
OBJECTIVE:
To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis.
METHODS:
The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed.
RESULTS:
Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037).
CONCLUSION
In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans
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Leukemia, Myeloid, Acute/diagnosis*
;
Mutation
;
Prognosis
;
Proto-Oncogene Proteins p21(ras)/genetics*
;
GTP Phosphohydrolases/genetics*
;
Retrospective Studies
;
Membrane Proteins/genetics*
;
Female
;
Male
;
Middle Aged
;
Adult
;
Aged
4.Clinical Characteristics and Prognostic Analysis of Peripheral T-Cell Lymphoma, Not Otherwise Specified.
Guo-Xiang CHEN ; Jian-Shu HAO ; Xue BAI ; Qing-Qing ZHANG ; Hai-Xia AN ; Xiu-Juan HUANG ; Yan-Qing SUN
Journal of Experimental Hematology 2025;33(3):753-759
OBJECTIVE:
To investigate the clinical characteristics and prognosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS).
METHODS:
Clinical data of 10 patients with PTCL-NOS in Gansu Provincial Hospital from May 2016 to June 2023 were collected. The treatment outcomes were evaluated, and the factors affecting prognosis were analyzed.
RESULTS:
The median age of onset for the 10 patients was 60.7 (47-75) years, with 7 males and 3 females. Nine cases received chemotherapy, while one case died suddenly after diagnosis, and the median course of chemotherapy was 6.9 (1-13) courses. Assessing the efficacy, 3 patients achieved complete remission (CR) while 7 patients showed progression. Age, sex, lactate dehydrogenase (LDH) level, Ki-67 and the presence of hemophagocytic lymphohistocytosis (HLH) were not statistically correlated with CR rate ( P >0.05). Patients with IPI score 3-5, and Ann Arbor stage III-IV had statistically lower CR rates (both P <0.05). Age, B symptoms, LDH level ,hemoglobin, Ki-67 index and PLR value were not statistically correlated with overall survival (OS) time ( P >0.05). Male, platelet <150×109/L, IPI score 3-5, Ann Arbor stage III-IV, presence of HLH, NLR≥4.05, and LMR <2.81 were statistically correlated with shorter OS (all P <0.05). Among the 10 patients, 3 cases have survived and are still in CR status, while 7 cases have died, with a median survival time of 7.5 (1-85) months.
CONCLUSIONS
Patients with IPI score 3-5 and Ann Arbor stage III-IV have low CR rate and poor prognosis. The OS of patients who are male, with platelet <150×109/L, IPI score 3-5, Ann Arbor stage III-IV, complication of HLH, NLR≥4.05, and LMR <2.81 is short, and prognosis is poor.
Humans
;
Lymphoma, T-Cell, Peripheral/diagnosis*
;
Male
;
Prognosis
;
Middle Aged
;
Female
;
Aged
5.Correlation Analysis of Inflammatory Indexes and Bone Marrow Cytological Characteristics with Prognosis in Patients with Hemophagocytic Lymphohistiocytosis.
Guo-Xiang CHEN ; Jian-Shu HAO ; Qing-Qing ZHANG ; Hai-Xia AN ; Yan-Qing SUN ; Xiu-Juan HUANG
Journal of Experimental Hematology 2025;33(4):1086-1093
OBJECTIVE:
To investigate the clinical characteristics and prognosis of patients with hemophagocytic lymphohistiocytosis (HLH).
METHODS:
Clinical data of 78 patients with HLH admitted to Gansu Provincial People's Hospital from January 2014 to May 2023 were collected, and the correlation between relevant indicators and patient prognosis was analyzed.
RESULTS:
Among the 78 HLH patients, there were 48 males and 30 females, with a median age of onset of 48 (1-84) years old; 26 patients were treated with chemotherapy, 44 patients were treated with glucocorticoids, immunoglobulin or cyclosporine, 5 patients received symptomatic treatment, 1 patient received plasma exchange, and 2 patients refused treatment. By the end of the follow-up, there were 39 survivors, 35 deaths, and 4 patients lost to follow-up. There was no significant correlation between sex, ferritin, triglycerides, hemophagocytosis, bone marrow cellularity, Epstein-Barr virus (EBV) infection, SUV value of PET-CT, alanine aminotransferase (ALT), interleukin-6 (IL-6), platelet-to-lymphocyte ratio (PLR) and overall survival (OS) of the patients (P >0.05). Patients with age≥60 years, neutrophil-to-lymphocyte ratio (NLR) >0.59, red cell distribution width-to-platelet ratio (RPR) >0.30, lymphocyte-to-monocyte ratio (LMR)≤2.74, red blood cell distribution width (RDW)>16.45%, tumor-associated HLH, aspartate aminotransferase (AST)≥148 U/L, procalcitonin (PCT)≥0.66 ng/ml, neutrophils (NEU) <2×109/L, fibrinogen (FIB)<1.85 g/L, lactate dehydrogenase (LDH)≥1 740 U/L, hemoglobin (Hb)<85 g/L, platelet (PLT)<57×109/L had significantly shorter OS, with statistical significance (P < 0.05). Multivariate analysis showed that LMR≤2.74, RDW>16.45%, LDH≥1 740 U/L, and NEU<2×109/L were independent risk factors affecting OS in HLH patients (P < 0.05).
CONCLUSION
Some blood-based inflammatory markers are significantly associated with OS in patients with HLH. NLR, RPR, LMR, RDW and PCT can be used to assess the prognosis of HLH patients, and RDW and LMR are independent factors affecting OS of HLH patients, which provide greater predictive value for prognosis. Hypercellular bone marrow in HLH patients may indicate a poor prognosis.
Humans
;
Lymphohistiocytosis, Hemophagocytic/diagnosis*
;
Prognosis
;
Female
;
Male
;
Middle Aged
;
Adult
;
Aged
;
Adolescent
;
Child
;
Child, Preschool
;
Infant
;
Young Adult
;
Bone Marrow/pathology*
;
Aged, 80 and over
;
Inflammation
6.Expression of METTL7B in Newly Diagnosed Patients with Acute Myeloid Leukemia and Its Influence on Prognosis.
Wen-Bang ZHANG ; Shu-Xia GUO ; Xiao-Juan ZHANG ; Huan-Jun LIU ; Meng-Yao LIU
Journal of Experimental Hematology 2025;33(5):1287-1292
OBJECTIVE:
To detect the expression of methyltransferase-like 7B ( METTL7B) in bone marrow specimens of patients with acute myeloid leukemia (AML), and to analyze its influence and significance on clinical diagnosis, treatment, and prognosis of AML patients.
METHODS:
Bone marrow specimens from 60 newly diagnosed AML patients were collected as the observation group, and bone marrow specimens from 20 iron-deficiency anemia (IDA) patients were collected as the control group. Clinical and pathological data of AML patients were also collected. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the expression of METTL7B in AML patients and IDA patients. Statistical analyses were performed to investigate the relationship between the expression level of METTL7B and clinical-pathological characteristics in AML patients, as well as the impact of METTL7B expression level on efficacy. Kaplan-Meier method was used to analyze the effect of METTL7B expression level on the overall survival time (OS) in AML patients. Meanwhile, a Cox proportional hazards regression model was constructed to identify the factors potentially affecting the prognosis of AML patients.
RESULTS:
Compared with the control group, the expression level of METTL7B was significantly upregulated in AML patients (P < 0.05). Compared with the low-expression group of METTL7B, the high-expression group had a higher proportion of patients with high white blood cell (WBC) count, poor prognosis, and ineffective treatment, and the differences were statistically significant (P < 0.05). The OS of patients in the high-expression group of METTL7B was significantly shorter than that in the low-expression group (P < 0.05). Multivariate Cox regression analysis showed that high WBC count, poor prognosis in prognosis stratification, and high expression of METTL7B were independent risk factors for the prognosis of AML patients (P < 0.05).
CONCLUSION
METTL7B is highly expressed in AML patients, and patients with high METTL7B expression exhibit shorter survival and poor prognosis. METTL7B is expected to serve as a new indicator for evaluating the prognosis of AML patients and may develop into a potential target for targeted treatment of AML in the future.
Humans
;
Leukemia, Myeloid, Acute/metabolism*
;
Prognosis
;
Methyltransferases/metabolism*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Proportional Hazards Models
7.Efficacy and prognostic factors of open surgical repair and endovascular repair in patients with ruptured abdominal aortic aneurysm.
Lei ZHANG ; Dexiang XIA ; Pengcheng GUO ; Xin LI ; Chang SHU
Journal of Central South University(Medical Sciences) 2025;50(7):1158-1166
OBJECTIVES:
Ruptured abdominal aortic aneurysm (rAAA) is a life-threatening vascular emergency with extremely high in-hospital mortality. Open surgical repair (OSR) was historically the only treatment option but is associated with substantial trauma and perioperative risk. In recent years, endovascular repair (EVAR) has gained widespread use due to its minimally invasive nature and faster recovery, becoming the preferred option for anatomically suitable patients in many centers. However, controversy remains regarding the long-term survival benefits of EVAR compared with OSR and key prognostic factors affecting outcomes. This study aims to evaluate the clinical efficacy of OSR and EVAR for rAAA and identify independent predictors of postoperative survival to guide clinical decision-making.
METHODS:
A retrospective analysis was conducted on 83 patients diagnosed with rAAA and treated surgically in the Department of Vascular Surgery, the Second Xiangya Hospital of Central South University, between January 2013 and December 2022. Patients were divided into an OSR group and an EVAR group based on surgical approach. Baseline clinical characteristics, perioperative data, and follow-up outcomes were compared between groups. Long-term survival was analyzed, and univariate and multivariate Cox proportional hazards regression models were used to determine independent prognostic factors.
RESULTS:
Among the 83 patients, 32 (38.6%) underwent OSR and 51 (61.4%) received EVAR, with the proportion of EVAR steadily increasing to nearly 80% in the most recent 5 years. Patients in the EVAR group were older [(68.76±8.57) years vs (60.59±13.24) years, P=0.012], and had a lower proportion of males (76.5% vs 96.9%, P=0.013). EVAR significantly reduced operating time [(181.86±69.87) min vs (291.09±60.33) min] and hospital stay [(12.14±6.31) days vs (16.22±7.89) days (P<0.05)], but total hospitalization costs were markedly higher [(208 735.84±101 394.19) yuan vs (84 893.35±40 668.56) yuan, P<0.001]. There were no significant differences between groups in 30-day mortality (15.6% vs 15.7%), aneurysm-related mortality (9.4% vs 11.7%), overall mortality (28.1% vs 29.4%), or re-intervention rate (0 vs 5.9%) (P>0.05). The median follow-up time was 54.6 months (range, 12-144 months). Kaplan-Meier survival analysis showed comparable cumulative survival rates between OSR and EVAR (82.7% vs 76.2%, P=0.420). Cox regression identified hyperlipidemia [hazard ratio (HR)=2.32, 95% confidence interval (CI) 1.28 to 4.19, P=0.005] and elevated preoperative serum creatinine (HR=3.33, 95% CI 1.69 to 6.55, P<0.001) as significant predictors of poor prognosis. Both factors remained independently associated with mortality in the multivariate model (hyperlipidemia: HR=2.02, 95% CI 1.10 to 3.70; elevated serum creatinine: HR=2.77, 95% CI 1.40 to 5.47; P<0.05).
CONCLUSIONS
EVAR offeres advantages in operative and recovery times, though its long-term survival outcomes are comparable to OSR. A history of hyperlipidemia and elevated preoperative creatinine levels are independent predictors of poor prognosis. Surgical approach should be chosen based on anatomical feasibility and patient condition, with close management of lipid levels and renal function to improve outcomes.
Humans
;
Aortic Aneurysm, Abdominal/mortality*
;
Endovascular Procedures/methods*
;
Retrospective Studies
;
Male
;
Female
;
Prognosis
;
Aged
;
Aortic Rupture/mortality*
;
Middle Aged
;
Treatment Outcome
;
Aged, 80 and over
8.Application advances of fractional flow reserve in endovascular treatment of lower-extremity arterial disease.
Lei ZHANG ; Jian QIU ; Dingxiao LIU ; Pengcheng GUO ; Dexiang XIA ; Chang SHU ; Xin LI
Journal of Central South University(Medical Sciences) 2025;50(7):1255-1262
Fractional flow reserve (FFR), an established modality for functionally assessing coronary artery disease, is increasingly applied to diagnose and manage lower extremity arterial disease. By incorporating functional parameters, FFR enhances revascularization precision by quantifying the hemodynamic impact of stenotic lesions, thereby overcoming limitations of conventional imaging. Key clinical applications in lower extremity disease include functional assessment in moderate intermittent claudication, post-vascular preparation strategy optimization, and predicting revascularization outcomes and complications. Advances in pressure wire and microcatheter systems, alongside non-invasive imaging-derived FFR techniques, are improving its feasibility and applicability. However, widespread adoption is challenged by the complex anatomy of the lower extremity arterial system, frequent severe calcification and diffuse disease, and a current lack of standardized FFR cutoff values. Promoting the standardized use of FFR is crucial for shifting the clinical management paradigm from anatomy-based repair toward functional reconstruction.
Humans
;
Lower Extremity/blood supply*
;
Peripheral Arterial Disease/diagnosis*
;
Fractional Flow Reserve, Myocardial
;
Endovascular Procedures/methods*
;
Intermittent Claudication/physiopathology*
9.Interleukin-33 Knockout Promotes High Mobility Group Box 1 Release from Astrocytes by Acetylation Mediated by P300/CBP-Associated Factor in Experimental Autoimmune Encephalomyelitis.
Yifan XIAO ; Liyan HAO ; Xinyi CAO ; Yibo ZHANG ; Qingqing XU ; Luyao QIN ; Yixuan ZHANG ; Yangxingzi WU ; Hongyan ZHOU ; Mengjuan WU ; Mingshan PI ; Qi XIONG ; Youhua YANG ; Yuran GUI ; Wei LIU ; Fang ZHENG ; Xiji SHU ; Yiyuan XIA
Neuroscience Bulletin 2025;41(7):1181-1197
High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals
;
Encephalomyelitis, Autoimmune, Experimental/metabolism*
;
Astrocytes/metabolism*
;
Interleukin-33/metabolism*
;
HMGB1 Protein/metabolism*
;
Acetylation
;
Mice, Knockout
;
Mice, Inbred C57BL
;
p300-CBP Transcription Factors/metabolism*
;
Mice
;
Spinal Cord/metabolism*
;
Cells, Cultured
;
Female
;
Signal Transduction
10.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione.
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):101068-101068
Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

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