1.Tongnao Decoction Promotes Angiogenesis and Alleviates Cerebral Ischemic Injury via PI3K/Akt/GSK-3β Signaling Pathway
Yan LIU ; Yang WU ; Wanhui PENG ; Jingyi CHEN ; Jiale GAN ; Li LI ; Yangjingyi XIA ; Yunze LI ; Zhaoyao CHEN ; Wenlei LI ; Minghua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):100-110
ObjectiveTo investigate the mechanisms of Tongnao decoction (TND) in mice with acute ischemic stroke (AIS). MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group, model group, TND low-dose group (1.86 g·kg-1), TND high-dose group (3.72 g·kg-1), and butylphthalide (NBP) group (10 mg·kg-1), with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis (PT). The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T2-weighted imaging (T2WI) was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin (HE) staining was used to observe histological changes in the cerebral cortex, and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging (LSCI) system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine (BrdU) and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), and their phosphorylation levels, as well as tight junction-related proteins zonula occludens-1 (ZO-1), Occludin, and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group, model group, TND low and high dose groups (0.16, 0.32 g·L-1) and NBP group (10 μmol·L-1), with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that, compared with the model group, the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time (P<0.05). HE staining and Nissl staining showed that, compared with the model group, the drug-treated groups exhibited reduced brain tissue damage, fewer scars, and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group (P<0.01), promoting angiogenesis. Meanwhile, compared with the model group, the drug-treated groups upregulated the expression levels of p-PI3K, p-Akt, p-GSK-3β, and tight junction proteins ZO-1, Occludin, and Claudin-5 (P<0.05,P<0.01), and increased the number of intersegmental vessels in zebrafish (P<0.05,P<0.01). ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway, thereby improving cerebral ischemic injury.
2.Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation.
Shengjie CUI ; Yanning GUO ; Yu FU ; Ting ZHANG ; Jieni ZHANG ; Yehua GAN ; Yanheng ZHOU ; Yan GU ; Eileen GENTLEMAN ; Yan LIU ; Xuedong WANG
International Journal of Oral Science 2025;17(1):35-35
Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund's complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young's modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
Animals
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NF-kappa B/metabolism*
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Temporomandibular Joint Disorders/pathology*
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Temporomandibular Joint Disc/metabolism*
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Rats
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Rats, Sprague-Dawley
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Disease Models, Animal
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Male
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Collagen/metabolism*
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Cells, Cultured
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Joint Dislocations/pathology*
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Interleukin-1beta
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Arthritis, Experimental
4.Development and Initial Validation of the Multi-Dimensional Attention Rating Scale in Highly Educated Adults.
Xin-Yang ZHANG ; Karen SPRUYT ; Jia-Yue SI ; Lin-Lin ZHANG ; Ting-Ting WU ; Yan-Nan LIU ; Di-Ga GAN ; Yu-Xin HU ; Si-Yu LIU ; Teng GAO ; Yi ZHONG ; Yao GE ; Zhe LI ; Zi-Yan LIN ; Yan-Ping BAO ; Xue-Qin WANG ; Yu-Feng WANG ; Lin LU
Chinese Medical Sciences Journal 2025;40(2):100-110
OBJECTIVES:
To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels.
METHODS:
The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT).
RESULTS:
The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049).
CONCLUSIONS
The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans
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Adult
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Male
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Attention/physiology*
;
Female
;
Middle Aged
;
Reproducibility of Results
;
Young Adult
;
Psychometrics
5.Efficacy and safety of CA280 cytokine adsorption column in treatment of acute-on-chronic liver failure
Yan HE ; Dakai GAN ; Xiaoqing ZHANG ; Tao LONG ; Xuezhen ZHANG ; Wei ZHANG ; Yizhen XU ; Yuyu ZENG ; Rui ZHOU ; Shuanglan LIU ; Xizi JIANG ; Yushi LU ; Molong XIONG ; Yunfeng XIONG
Journal of Clinical Hepatology 2025;41(10):2093-2101
ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange (LPE) in patients with acute-on-chronic liver failure (ACLF). MethodsA prospective cohort study was designed, and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment, the patients in the DPMAS+LPE group received DPMAS and LPE treatment, and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results, liver function parameters, renal function markers, electrolytes, coagulation function parameters, cytokines, adverse events, and 28-day prognosis before surgery (baseline), during surgery (DPMAS or CA280), and after surgery (after sequential LPE treatment). The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group, and the independent-samples t test was used for comparison between groups; the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group, and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups, and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment, the ACLF patients had significant reductions in the levels of cytokines (IL-6, IL-8, IL-10, TNF-α, and IFN-γ), liver function parameters (ALT, AST, ALP, TBil, DBil, Alb, and glutathione reductase), and the renal function marker urea nitrogen (all P<0.05), and in terms of coagulation function parameters, there were significant increases in prothrombin time, activated partial thromboplastin time (APTT), thrombin time, and international normalized ratio (INR) and significant reductions in prothrombin activity (PTA) and fibrinogen (FIB) (all P<0.05). Compared with the DPMAS+LPE group, the CA280+LPE group showed better improvements in the serum cytokines IL-8 (Z=-2.63, P=0.009), IL-10 (Z=-3.94, P<0.001), and TNF-α (Z=-1.53, P=0.023), and the two artificial liver support systems had a similar effect in improving liver function (ALT, AST, GGT, GR, TBil, and DBil) (all P >0.05), but the CA280+LPE group showed a significantly greater reduction in Alb (Z=-2.08, P=0.037). CA280+LPE was more effective in reducing uric acid (Z=-2.97, P=0.003). Compared with DPMAS+LPE, CA280+LPE treatment resulted in a significant reduction in INR (Z=-4.01, P<0.001), a significant increase in APTT (Z=-2.53, P=0.011), and significant greater increases in PTA (Z=-6.28, P<0.001) and FIB (Z=-3.93, P<0.001). There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups (all P>0.05). The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC (r=0.22, P=0.042), TBil (r=0.29, P=0.005), and FIB (r=-0.33, P=0.003); IL-8 was positively correlated with APTT (r=0.37, P<0.001) and INR (r=0.25, P=0.013); TNF-α was significantly correlated with WBC (r=0.40, P<0.001) and TBil (r=0.34, P<0.001). ConclusionCompared with DPMAS, CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients, but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients, but further studies are needed to verify its long-term efficacy.
6.MR intravoxel incoherent motion for analysis of placental microcirculation and microstructures in plateau area of late pregnancy induced hypertension and normal middle and late pregnancy women
Fei LIU ; Zhanyue YAN ; Zhengning GAN ; Chenghuan LIU ; Shenglan WANG ; Linkui ZHANG ; Gang LIU
Chinese Journal of Medical Imaging Technology 2025;41(9):1554-1557
Objective To observe the value of MR intravoxel incoherent motion(IVIM)for analyzing placental microcirculation and microstructures in plateau area of late pregnancy induced hypertension(PIH)and normal middle and late pregnancy.Methods Totally 26 cases of PIH in late-trimester of pregnancy(group A)and 46 normal pregnant women(including 18 normal middle-trimester[group B]and 28 normal late-trimester[group C])in plateau area were retrospectively analyzed.The perfusion fraction(f),true diffusion coefficient(D)and pseudo-diffusion coefficient(D*)values of the entire placenta and the fetal side,maternal side and central region of placenta were obtained based on MR IVIM data,intra-and inter-group comparisons were conducted.Pearson correlation analysis was used to explore the relationships of placental IVIM parameters and maternal age,gestational age,estimated fetal weight(EFW)and neonatal birth weight.Results Except for f value of placental maternal side was higher than of fetal side in group C(P<0.05),no significant difference was found in pairwise comparisons of IVIM parameters between different placental regions within each group(all P>0.05).f value of the entire placenta and its fetal side,as well as D value of the entire placenta and its maternal side in group A were all higher than those in group C(all adjusted P<0.05).The f and D* values of the entire placenta,f,D and D*values of its maternal side,as well as f and D* values of the fetal side in group C were all higher than those in group B(all adjusted P<0.05).In group C,f value of placental maternal side was negatively correlated with both gestational age and EFW(r=-0.441,-0.579,both P<0.01).Conclusion MR IVIM could be used to non-invasively assess placental microcirculation and microstructures in plateau area of late PIH and normal middle and late pregnancy women.
7.LncRNA GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and Invasion of lung squamous carcinoma cells
Yu-ning HU ; Yan-lei GE ; Ye JIN ; Jun-qing GAN ; Wei-nan YAO ; Ya-nan WU ; Xuan ZHENG ; Zi-qing LIU ; Xin SU ; Guo-gui SUN
Chinese Pharmacological Bulletin 2025;41(8):1531-1541
Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P<0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P<0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P<0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P<0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P<0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P<0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P>0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.
8.Clinical effect of indocyanine green angiography-assisted design and harvest of expanded flaps for scar reconstruction
Yanan HU ; Tingjun XIE ; Yuanbo LIU ; Shan ZHU ; Zengjie YANG ; Jia TIAN ; Cheng GAN ; Hu JIAO ; Shanshan LI ; Zixiang CHEN ; Lu ZHOU ; Bing HAN ; Shengyang JIN ; Yan ZENG ; Miao WANG ; Mengqing ZANG
Chinese Journal of Burns 2025;41(4):341-347
Objective:To investigate the clinical effect of indocyanine green angiography (ICGA)-assisted design and harvest of expanded flaps for scar reconstruction.Methods:This study was a retrospective observational study. From April 2019 to August 2023, 19 patients with scars (8 males, 11 females; aged 3-38 years) treated at the Plastic Surgery Hospital of Peking Union Medical College and Chinese Academy of Medical Sciences met the inclusion criteria. The scars were distributed on the head, face, trunk, and extremities. In stage Ⅰ surgery, skin soft tissue expanders were implanted in suitable areas around the scars for skin soft tissue expansion. In stage Ⅱ surgery, the scar tissue was excised, resulting in wound areas ranging from 100 to 210 cm 2, and expanded flaps were designed. ICGA was used to identify target perforators and their accompanying veins, and the flap design was adjusted to ensure the inclusion of complete arterial and venous axes. The expanded flap with an area of 120 to 240 cm2 was harvested using unilateral back-cut technique and transferred to the recipient site, and the donor site wound was sutured directly. The durations of the arterial and venous phases of ICGA during flap design were recorded. The length-to-width ratios of the back-cut flaps were calculated for different regions. After stage Ⅱ surgery, the blood perfusion and survival of the flap, the wound healing at the donor site, and the occurrence of complications were observed. During follow-up, the appearance, color, and texture of the patient's flap were observed. Results:The arterial phase of ICGA lasted 10-27 (18±5) s, and the venous phase lasted 78-116 (100±10) s. The length-to-width ratios of the back-cut flaps were 1.22±0.32, 1.63±0.12, and 1.15±0.21 for the head and neck, trunk, and limb regions, respectively. After stage Ⅱ surgery, one patient had a large area of insufficient blood perfusion in the flap. By comparing ICGA images before and after flap transfer, the sutures at the oral commissure were loosened, the blood flow of the flap was restored. The blood perfusion of the flaps in other patients was good. All flaps survived completely, with well-healed donor site wounds and no complications. During 0.5-14.0 months of follow-up, all flaps of patients demonstrated excellent appearance, with color and texture matching the surrounding skin.Conclusions:As a means of superficial blood flow visualization, ICGA can not only clearly show the microvascular distribution of the expanded flap before operation, assist in optimizing the design of the flap, but also evaluate the blood perfusion of the flap after operation, reduce the occurrence of complications, and provide a full-process navigation for the harvesting of expanded flaps, thereby improving the safety of flap transfer for scar reconstruction.
9.Anti-inflammatory and anti-apoptotic effects and mechanism of total flavonoids of hawthorn leaves on rat intestinal epithelial cells
Kai WANG ; Pei LIU ; Kexin QI ; Jingyi WANG ; Chenlu SUN ; Danning SHI ; Hongyue CHEN ; Daoling HE ; Yan ZHU ; Ling GAN
Chinese Journal of Veterinary Science 2025;45(7):1450-1457
This study aims to investigate the anti-inflammatory and anti-apoptotic effects of total flavonoids of hawthorn leaves(TFHL)on lipopolysaccharide(LPS)-induced inflammatory injury in rat intestinal epithelial(IEC-6)cells,as well as the underlying mechanisms.An in vitro inflam-mation model was first established by treating IEC-6 cells with lipopolysaccharide(LPS).IEC-6 cells were then incubated with three concentrations of TFHL for 24 h prior to a further 24 h LPS treatment.RT-qPCR was used to quantify mRNA levels of the inflammatory genes COX-2 and iN-OS,while Western blotting was used to assess protein levels of the apoptotic markers Bax,cleaved Caspase-3,Bcl-2,and the JNK/p-JNK signaling pathway.Finally,cells were pretreated with TFHL and/or the JNK inhibitor SP600125 for 24 h before LPS exposure for 24 h,in order to evaluate the combined effects of TFHL and SP600125 on LPS-induced inflammatory cytokine expression and apoptotic protein levels in IEC-6 cells.The results showed that,compared with the LPS group,the mRNA level of COX-2 and iNOS in the 2.5,5.0,10.0 mg/L TFHL group and the Bax and Caspase-3 protein levels decreased significantly(P<0.01),and the Bcl-2 protein level was significantly higher(P<0.01),p-JNK protein level and p-JNK/JNK ratio decreased significantly(P<0.01);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+LPS group de-creased significantly(P<0.01),Bax,and Caspase-3 protein levels decreased significantly(P<0.01),and the level of Bcl-2 protein increased significantly(P<0.05);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+SP600125 group decreased significantly(P<0.01),Bax and Caspase-3 protein levels decreased significantly(P<0.01),and Bcl-2 protein level increased significantly(P<0.01).These findings indicate that TFHL exerts anti-inflammato-ry and anti-apoptotic effects in LPS-challenged IEC-6 cells by inhibiting the JNK signaling path-way.
10.Mechanism of action of long non-coding RNA AC087388.1 targeting PABPC1 on esophageal squamous cell carcinoma
Han ZHONG ; Yan-lei GE ; Jun-qing GAN ; Ye JIN ; Xuan ZHENG ; Zi-qing LIU ; Guo-gui SUN
Chinese Pharmacological Bulletin 2025;41(5):926-935
Aim To explore the roles and mechanisms of long non-coding RNA(lncRNA)AC087388.1 and poly(A)binding protein cytoplasmic 1(PABPC1)in esophageal squamous cell carcinoma(ESCC).Meth-ods The expression level of AC087388.1 in ESCC tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and fluorescence in situ hybridization experiments and its clinical relevance was analyzed.Cell counting kit-8(CCK-8),clone formation,scratch and Transwell inva-sion assays were used to detect the effects of knock-down of AC087388.1 on the cell viability,prolifera-tion,migratory,and invasion of ESCC cells respectively ability,and sub-localization in cells.RNA pull down and Western blot experiments were employed to verify the interaction between AC087388.1 and PABPC1 in ESCC cells.Salvage experiments were performed to detect the effect of AC087388.1 targeting PABPC1 on ESCC cells.Results AC087388.1 was highly ex-pressed in ESCC tissues and cells and positively corre-lated with clinical stage of ESCC patients,mainly local-ized in cytoplasm.Knockdown AC087388.1 inhibited ESCC cell viability,proliferation,migration and inva-sionability.PABPC1 was selected from the results of RNA Pull Down-MS experiments for subsequent experi-ments,and AC087388.1 was verified to bind to PAB-PC1 by RNA Pull Down and Western blot experiments.Overexpression of AC087388.1 was verified by rescue experiment to reverse the effects of knockdown of PAB-PC1 on ESCC cell viability,proliferation,migration and invasion.Conclusions High expression of AC087388.1 correlates with clinical stage and may be a risk factor for ESCC progression.AC087388.1 pro-motes the cell viability,proliferation,migration and in-vasive ability of ESCC cells by targeting PABPC1,which may be a novel biomarker for the diagnosis and treatment of ESCC.

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