1.Effect of CYFIP1 on proliferation and apoptosis of colorectal cancer cell HT29
Fu-long YU ; Liang LI ; Hao QIANG ; Hui YUAN ; Song WANG ; Xiao-hu CHENG ; Run-ben JIANG ; Ya-ru YANG ; Zhi-ning LIU
Chinese Pharmacological Bulletin 2025;41(1):116-121
Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P<0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P<0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P<0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P<0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.
2.Combining diffusion tensor imaging with motor evoked potentials in the evaluation of upper limb motor function post-stroke
Ying LI ; Yaxin YANG ; Haifeng YUAN ; Ben MA ; Zhongheng WU ; Jing FU ; Qiaojun ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(1):13-18
Objective:To observe effectiveness of combining diffusion tensor imaging (DTI) with motor evoked potentials (MEPs) in evaluating the upper limb motor functioning of stroke survivors.Methods:Thirty-seven stroke survivors with upper limb motor dysfunction were selected. At the 4th, 12th and 24th week after their onset, each was were assessed using Fugl-Meyer Upper Limb (FMA-UE) scoring, the National Institutes of Health stroke scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index (BI) and hemiplegic hand function classification. DTI was also applied and MEPs were measured. The patients were divided into an MEP positive group and an MEP negative group according to the existence of the MEP waveform. The DTI and MEP parameters were correlated with the FMA-UE scores, linear regressions were evaluated and a receiver operating characteristics curve was prepared to estimate the utility of DTI in predicting hand function. The sensitivity and specificity of MEPs in predicting hand function recovery were evaluated.Results:The asymmetry index (FAa) of the average anisotropy score of the posterior limb of the internal capsule and the FAa of the cerebral peduncle were both significantly correlated with the FMA-UE scores at the 12th and 24th weeks. The best cut-off points for predicting functional recovery of a patient′s hand were 0.155 for the FAa of the posterior limb of the internal capsule and 0.145 for the cerebral peduncle. Among the 37 patients, the MEPs of 8 (the MEP positive group) could be extracted, and their hand functions recovered completely. The sensitivity of the MEPs in predicting the complete recovery of hand function was 80% with 100% specificity. The linear regression analysis showed 77% prediction accuracy for the FAa and MEPs of the cerebral peduncle for upper limb motor function at the 24th week after onset. In the MEP negative group, two patients completely recovered their hand function, with one′s FAa less than 0.145, and the other′s more than 0.145. When the MEP was negative, the sensitivity of DTI in predicting the recovery of hand function was 50% with 81.5% specificity.Conclusions:DTI combined with MEPs can be used as an index to evaluate the prognosis of upper limb motor function in stroke patients.
3.Combining diffusion tensor imaging with motor evoked potentials in the evaluation of upper limb motor function post-stroke
Ying LI ; Yaxin YANG ; Haifeng YUAN ; Ben MA ; Zhongheng WU ; Jing FU ; Qiaojun ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(1):13-18
Objective:To observe effectiveness of combining diffusion tensor imaging (DTI) with motor evoked potentials (MEPs) in evaluating the upper limb motor functioning of stroke survivors.Methods:Thirty-seven stroke survivors with upper limb motor dysfunction were selected. At the 4th, 12th and 24th week after their onset, each was were assessed using Fugl-Meyer Upper Limb (FMA-UE) scoring, the National Institutes of Health stroke scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index (BI) and hemiplegic hand function classification. DTI was also applied and MEPs were measured. The patients were divided into an MEP positive group and an MEP negative group according to the existence of the MEP waveform. The DTI and MEP parameters were correlated with the FMA-UE scores, linear regressions were evaluated and a receiver operating characteristics curve was prepared to estimate the utility of DTI in predicting hand function. The sensitivity and specificity of MEPs in predicting hand function recovery were evaluated.Results:The asymmetry index (FAa) of the average anisotropy score of the posterior limb of the internal capsule and the FAa of the cerebral peduncle were both significantly correlated with the FMA-UE scores at the 12th and 24th weeks. The best cut-off points for predicting functional recovery of a patient′s hand were 0.155 for the FAa of the posterior limb of the internal capsule and 0.145 for the cerebral peduncle. Among the 37 patients, the MEPs of 8 (the MEP positive group) could be extracted, and their hand functions recovered completely. The sensitivity of the MEPs in predicting the complete recovery of hand function was 80% with 100% specificity. The linear regression analysis showed 77% prediction accuracy for the FAa and MEPs of the cerebral peduncle for upper limb motor function at the 24th week after onset. In the MEP negative group, two patients completely recovered their hand function, with one′s FAa less than 0.145, and the other′s more than 0.145. When the MEP was negative, the sensitivity of DTI in predicting the recovery of hand function was 50% with 81.5% specificity.Conclusions:DTI combined with MEPs can be used as an index to evaluate the prognosis of upper limb motor function in stroke patients.
4.Effect of CYFIP1 on proliferation and apoptosis of colorectal cancer cell HT29
Fu-long YU ; Liang LI ; Hao QIANG ; Hui YUAN ; Song WANG ; Xiao-hu CHENG ; Run-ben JIANG ; Ya-ru YANG ; Zhi-ning LIU
Chinese Pharmacological Bulletin 2025;41(1):116-121
Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P<0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P<0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P<0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P<0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.
5.Therapeutic effect of TURP for prostatic abscesses primarily presenting as urinary retention in the aged males
Ben LIU ; Pengfei QI ; Dewang FU ; Qingyue SI ; Chenxi YU ; Zhifu HAN
Chinese Journal of Urology 2024;45(10):756-760
Objective:To investigate the clinical characteristics of prostatic abscesses (PA)primarily presenting as urinary retention in the elderly patients and the therapeutic effect of TURP.Methods:A retrospective analysis was conducted on the case records of four elderly patients with PA who presented primarily with urinary retention and were admitted to our hospital between July 2020 and August 2022. The median age of the four patients was 68.0 (62.0, 77.0) years, all of whom were admitted to the hospital due to progressive difficulty of urination and inability to urinate. All four patients exhibited chills and high fever, with three cases presenting prior to admission and one case post-admission. One patient developed secondary sepsis, and 2 patients experienced perineal pain. Two patients had a history of diabetes, and 2 had a history of hypertension. The rectal digital examination of these four patients revealed prostate enlargement, with 2 cases of tenderness and one case of fluctuation sensation on the prostate. Blood and urine bacterial cultures were carried out in 4 patients, of which 3 patients were positive of blood culture with 2 cases of Escherichia coli and one case of Klebsiella pneumoniae, 2 patients were positive of the urine culture with one case of Escherichia coli and one case of Klebsiella pneumoniae, and one patient was negative of blood and urine culture.Serum C-reactive protein (CRP)and procalcitonin (PCT) increased in these 4 patients, with 118-190 mg/L and 1.39-13.45 ng/ml respectively. One of the 4 patients had elevated serum PSA levels, with a value of 16.95 ng/L, while the remaining 3 patients had normal serum PSA levels. The median international prostate symptom score (IPSS) score before surgery was 31.5(28.7, 34.3) points for these 4 patients, and the median quality of life (QOL) score was 5.0(4.2, 5.8) points. The transabdominal ultrasound examination of these 4 patients showed that the prostate was enlarged and the echo of the prostate was uneven, and the hypoechoic area in the prostate was found in 2 cases. On plain CT scan of the prostate in these cases, the prostate was enlarged, and there was an area of uneven reduction in density. MRI plain scan of the prostate in 2 cases showed abscess in the peripheral zone of the prostate. Among the 4 cases of PA, 3 cases were diagnosed before operation. The size of abscess was 1.7-5.8 cm, including one case of multiple abscess. Another case of PA was found during TURP for benign prostatic hyperplasia. Four patients were undergoing TURP after antibiotic treatment. During the operation, the pus cavity was found at the prostatic capsule, and the pus cavity wall at the urethral side was removed to make the pus cavity fully open. Three-chamber F20 Foley catheter was placed in the urethra eventually.Results:The operation was successfully completed in these 4 patients, and the operation time was 30 to 90 minutes. Postoperative pathology reported benign prostatic hyperplasia with acute/chronic inflammatory cell infiltration. One patient developed fever on the day after operation, with the highest temperature of 38.6 ℃, and improved after pharmaceutical treatment. Urinary catheter was retained for 5 days postoperatively. Five days after surgery, the urinary catheter was removed and all 4 patients had unobstructed urination. One patient experienced transient urinary incontinence caused by urinary tract infection, which improved after 2 weeks of treatment with increased water intake and oral antibiotics. One month after the operation, the abscess cavity of all patients was completely disappeared and urination was smooth. One-month postoperative follow-up revealed complete resolution of abscess cavities in all patients by prostate CT. The median postoperative IPSS was 13.5(8.5, 17.0)( P=0.0286), and the median QOL score was 1.0(0.3, 1.8)( P=0.0284), both showing statistically significant differences compared to preoperative values. Over the follow-up period ranging from 19 to 44 months, no abscess recurrence was noted in the 4 cases, and retrograde ejaculation was noted in 2 cases. Complications such as urethral stricture, urinary incontinence, and urinary retention did not occur. One patient developed epididymitis and orchitis 6 weeks post-surgery, which improved following 2 weeks of conservative treatment. Conclusions:The symptoms of elderly PA patients primarily presenting as urinary retention were severe. TURP can relieve the symptoms of lower urinary tract obstruction while draining the pus cavity, and the therapeutic effect is satisfactory.
6.Three-dimensional finite element analysis of lumbar disc herniation under different body positions
Ben-Jing YIN ; Yu LU ; Fu-Tao JI ; Rong-Neng QIU ; Yuan-Yang XIE ; Ge CHEN ; Tian-Li XU ; Chao-Yu BAO ; Ju-Bao LI
China Journal of Orthopaedics and Traumatology 2024;37(6):599-604
Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.
7.Effects of integrin αvβ6 on lipidomics metabolism in relation to tumor progression for colon cancer
Ben-Jia LIANG ; Yang-Bin FU ; Jin-Tao YU ; Jun WANG ; Jun NIU ; Ming-Liang ZHOU
Chinese Journal of Current Advances in General Surgery 2024;27(9):678-683
Objective:To investigate the effect of integrin αvβ6 on lipid metabolism in colon cancer cells;to identify potential metabolic biomarkers for the diagnosis of colon cancer.Meth-ods:Liquid chromatography-mass spectrometry(LC-MS)-based lipidomic analysis was utilized to investigate the effects of αvβ6 on the changes in SW480 metabolism in colon cancer cell lines.The partial least squares discriminant analysis model showed different lipid profiles in Integrin αvβ6 over-expressed or low-expressed SW480.Results:After Integrin αvβ6 overexpression,a total of 252 lipids showed significant differences in SW480 cells,of which 138 showed up-regulation and 114 showed down-regulation.Moreover,the Methyl phosphatidylcholine(MePC),phosphatidyl-choline(PC),phosphatidylethanolamine(PE)and triglycerides(TG)were also found to have good diagnostic potential in αvβ6 overexpressing cancer cells.Conclusion:Integrin αvβ6 may promote cancer cell invasivness and metastasis by regulating pathways of dysregulated lipid metabolism.These results may provide potential clues to the molecular mechanisms of Integrin αvβ6 on colon cancer cells.
8.Therapeutic effect of TURP for prostatic abscesses primarily presenting as urinary retention in the aged males
Ben LIU ; Pengfei QI ; Dewang FU ; Qingyue SI ; Chenxi YU ; Zhifu HAN
Chinese Journal of Urology 2024;45(10):756-760
Objective:To investigate the clinical characteristics of prostatic abscesses (PA)primarily presenting as urinary retention in the elderly patients and the therapeutic effect of TURP.Methods:A retrospective analysis was conducted on the case records of four elderly patients with PA who presented primarily with urinary retention and were admitted to our hospital between July 2020 and August 2022. The median age of the four patients was 68.0 (62.0, 77.0) years, all of whom were admitted to the hospital due to progressive difficulty of urination and inability to urinate. All four patients exhibited chills and high fever, with three cases presenting prior to admission and one case post-admission. One patient developed secondary sepsis, and 2 patients experienced perineal pain. Two patients had a history of diabetes, and 2 had a history of hypertension. The rectal digital examination of these four patients revealed prostate enlargement, with 2 cases of tenderness and one case of fluctuation sensation on the prostate. Blood and urine bacterial cultures were carried out in 4 patients, of which 3 patients were positive of blood culture with 2 cases of Escherichia coli and one case of Klebsiella pneumoniae, 2 patients were positive of the urine culture with one case of Escherichia coli and one case of Klebsiella pneumoniae, and one patient was negative of blood and urine culture.Serum C-reactive protein (CRP)and procalcitonin (PCT) increased in these 4 patients, with 118-190 mg/L and 1.39-13.45 ng/ml respectively. One of the 4 patients had elevated serum PSA levels, with a value of 16.95 ng/L, while the remaining 3 patients had normal serum PSA levels. The median international prostate symptom score (IPSS) score before surgery was 31.5(28.7, 34.3) points for these 4 patients, and the median quality of life (QOL) score was 5.0(4.2, 5.8) points. The transabdominal ultrasound examination of these 4 patients showed that the prostate was enlarged and the echo of the prostate was uneven, and the hypoechoic area in the prostate was found in 2 cases. On plain CT scan of the prostate in these cases, the prostate was enlarged, and there was an area of uneven reduction in density. MRI plain scan of the prostate in 2 cases showed abscess in the peripheral zone of the prostate. Among the 4 cases of PA, 3 cases were diagnosed before operation. The size of abscess was 1.7-5.8 cm, including one case of multiple abscess. Another case of PA was found during TURP for benign prostatic hyperplasia. Four patients were undergoing TURP after antibiotic treatment. During the operation, the pus cavity was found at the prostatic capsule, and the pus cavity wall at the urethral side was removed to make the pus cavity fully open. Three-chamber F20 Foley catheter was placed in the urethra eventually.Results:The operation was successfully completed in these 4 patients, and the operation time was 30 to 90 minutes. Postoperative pathology reported benign prostatic hyperplasia with acute/chronic inflammatory cell infiltration. One patient developed fever on the day after operation, with the highest temperature of 38.6 ℃, and improved after pharmaceutical treatment. Urinary catheter was retained for 5 days postoperatively. Five days after surgery, the urinary catheter was removed and all 4 patients had unobstructed urination. One patient experienced transient urinary incontinence caused by urinary tract infection, which improved after 2 weeks of treatment with increased water intake and oral antibiotics. One month after the operation, the abscess cavity of all patients was completely disappeared and urination was smooth. One-month postoperative follow-up revealed complete resolution of abscess cavities in all patients by prostate CT. The median postoperative IPSS was 13.5(8.5, 17.0)( P=0.0286), and the median QOL score was 1.0(0.3, 1.8)( P=0.0284), both showing statistically significant differences compared to preoperative values. Over the follow-up period ranging from 19 to 44 months, no abscess recurrence was noted in the 4 cases, and retrograde ejaculation was noted in 2 cases. Complications such as urethral stricture, urinary incontinence, and urinary retention did not occur. One patient developed epididymitis and orchitis 6 weeks post-surgery, which improved following 2 weeks of conservative treatment. Conclusions:The symptoms of elderly PA patients primarily presenting as urinary retention were severe. TURP can relieve the symptoms of lower urinary tract obstruction while draining the pus cavity, and the therapeutic effect is satisfactory.
9.Effect of acupotomy on the fat infiltration degree of lumbar multifidus muscle in patients with lumbar disc herniation after percutaneous transforaminal endoscopic discectomy.
Yu-Xian ZHONG ; Yu DING ; Ben-Sheng FU ; Guang-Hao MA ; Hong-Peng CUI ; Ting-Ting CHEN ; Ling-Zhi PAN ; Qian LIU ; Hang-Chen XU ; Cheng-Xin LI ; Ling GUAN
Chinese Acupuncture & Moxibustion 2023;43(2):153-157
OBJECTIVE:
To observe the effect of acupotomy on the fat infiltration degree of lumbar multifidus muscle (LMM) in patients with lumbar disc herniation after percutaneous transforaminal endoscopic discectomy (PTED).
METHODS:
A total of 104 patients with lumbar disc herniation treated with PTED were randomly divided into an observation group (52 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). Patients of both groups received rehabilitation training of two weeks 48 h after PTED treatment. The observation group was treated with acupotomy (L3-L5 Jiaji [EX-B 2]) once within 24 h after PTED. In the two groups, the fat infiltration cross sectional area (CSA) of LMM was compared before and 6 months after PTED, the visual analogue scale (VAS) score and Oswestry disability index (ODI) score were observed before and 1, 6 months after PTED. The correlation between fat infiltration CSA of LMM in each segment and VAS score was analyzed.
RESULTS:
Six months after PTED, the fat infiltration CSA of LMM in L4/L5 and the total L3-S1 segments of the observation group was lower than that before PTED (P<0.05), and the fat infiltration CSA of LMM in L4/L5 of the observation group was lower than the control group (P<0.01). One month after PTED, the ODI and VAS scores of the two groups were lower than those before PTED (P<0.01), and those in the observation group were lower than the control group (P<0.05). Six months after PTED, the ODI and VAS scores of the two groups were lower than those before PTED and 1 month after PTED (P<0.01), and those in the observation group were lower than the control group (P<0.01). There was a positive correlation between the fat infiltration CSA of LMM in the total L3-S1 segments and VAS scores in the two groups before PTED (r = 0.64, P<0.01). Six months after PTED, there was no correlation between the fat infiltration CSA of LMM in each segment and VAS scores in the two groups (P>0.05).
CONCLUSION
Acupotomy can improve the fat infiltration degree of LMM, pain symptoms and activities of daily living in patients with lumbar disc herniation after PTED.
Humans
;
Intervertebral Disc Displacement
;
Activities of Daily Living
;
Paraspinal Muscles
;
Treatment Outcome
;
Lumbar Vertebrae
;
Retrospective Studies
;
Endoscopy
;
Diskectomy
;
Acupuncture Therapy
10.Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-β axis.
Ben-Sheng DONG ; Fu-Qun LIU ; Wen-Na YANG ; Xiao-Dong LI ; Miao-Juan SHI ; Mao-Rong LI ; Xiu-Li YAN ; Hui ZHANG
Journal of Integrative Medicine 2023;21(1):47-61
OBJECTIVE:
Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.
METHODS:
The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.
RESULTS:
Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment.
CONCLUSION
Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.
Humans
;
Transforming Growth Factor beta/pharmacology*
;
Transforming Growth Factor beta1/metabolism*
;
RNA, Long Noncoding/pharmacology*
;
Drugs, Chinese Herbal/pharmacology*
;
MicroRNAs/genetics*
;
Hepatic Stellate Cells/pathology*
;
Liver Cirrhosis/metabolism*
;
Cell Proliferation
;
Transforming Growth Factors/pharmacology*

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