1.Lectin-like oxidized low-density lipoprotein receptor-1 regulates cardiac fibroblasts fibrosis induced by high glucose through glycogen synthase kinase-3β/signal transducer and activator of transcription 3 pathway
Yaqian LIU ; Jing LIU ; Limin TIAN ; Zhihong WANG ; Huiling SI ; Yajuan ZHANG ; Jumei QIU ; Qidang DUAN ; Yanyan ZHANG ; Na ZHANG ; Wenshu ZHAO ; Xia WANG ; Qi ZHANG
Chinese Journal of Diabetes 2024;32(5):373-379
Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.
2.LOX-1 promotes hyperglycemia-induced phagocytosis dysfunction of BV2 microglia through the β-catenin/ATF6α pathway
Yajuan ZHANG ; Jing LIU ; Limin TIAN ; Na ZHANG ; Yanyan ZHANG ; Yaqian LIU ; Huiling SI ; Wenshu ZHAO ; Jumei QIU ; Qi ZHANG
Chinese Journal of Diabetes 2024;32(6):450-457
Objective To investigate the molecular mechanism of lectin-like oxidized low-density lipoprotein receptor 1(LOX-1)in the regulation of high glucose induced phagocytosis dysfunction of mouse microglia(BV2 microglia).Methods BV2 cells were cultured in vitro,lentivirus LOX-1RNAi vector(LV-LOX-1)and lentivirusempty vector(LV-Con)were constructed and divided into normal control(NC)group,HG group,LV-LOX-1 group and LV-Con group.After infecting BV2 cells with LV-LOX-1 and LV-Con,the cells were cultured with 25 mmol/L glucose for 24 h,and then divided into HG+LV-LOX-1 group and HG+LV-Con group.After treatment of HG+LV-LOX-1 and HG+LV-Con infected BV2 microglia with 15 μmol/L FH535(β-catenin inhibitor)and AEBSF(ATF6α inhibitor)for 24 h,respectively,they were denoted as HG+LV-LOX-1+FH535 group,HG+LV-Con+FH535 group,HG+LV-LOX-1+AEBSF group,and HG+LV-Con+AEBSF group.Transfection efficiency was determined by fluorescence microscopy,RT-PCR and Western blot.Cell viability was detected b CCK-8.RT-PCR and Western blot were used to detect the mRNA and protein expression of LOX-1,β-catenin,ATF6α and milk fat globular-surface growth factor Ⅷ(MFG-E8)in each group.Results After 72 h of LV-LOX-1 infection,the cells in LV-LOX-1 and LV-Con groups showed a lot of green fluorescence,but not in NC group.Compared with NC group,the mRNA and protein expression of LOX-1 and ATF6α were increased(P<0.05),while the mRNA and protein expression of MFG-E8 and β-catenin decreased in HG group(P<0.05).Compared with HG+LV-Con group,the mRNA and protein expression of LOX-1 and ATF6α were decreased(P<0.05),while the mRNA and protein expression of MFG-E8 and β-catenin increasedin HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,the mRNA and protein expressions of MFG-E8 and β-catenin were decreased(P<0.05),and the mRNA and protein expressions of ATF6α and p-β-catenin and p-ATF6α were increased in HG+LV-LOX-1+FH535 group(P<0.05).Compared with HG+LV-LOX-1 group,the mRNA and protein expression were increased(P<0.05),ATF6α mRNA and protein expression and p-ATF6α protein expression were decreased MFG-E8 in HG+LV-LOX-1+AEBSF group(P<0.05).Conclusions LOX-1,MFG-E8,β-catenin and ATF6α are involved in the regulation of phagocytosis of BV2 cells.LOX-1 promotes the phagocytosis dysfunction of BV2 microglia induced by high glucose through β-catenin/ATF6α signaling pathway.
3.A national questionnaire survey on endoscopic treatment for gastroesophageal varices in portal hypertension in China
Xing WANG ; Bing HU ; Yiling LI ; Zhijie FENG ; Yanjing GAO ; Zhining FAN ; Feng JI ; Bingrong LIU ; Jinhai WANG ; Wenhui ZHANG ; Tong DANG ; Hong XU ; Derun KONG ; Lili YUAN ; Liangbi XU ; Shengjuan HU ; Liangzhi WEN ; Ping YAO ; Yunxiao LIANG ; Xiaodong ZHOU ; Huiling XIANG ; Xiaowei LIU ; Xiaoquan HUANG ; Yinglei MIAO ; Xiaoliang ZHU ; De'an TIAN ; Feihu BAI ; Jitao SONG ; Ligang CHEN ; Yingcai MA ; Yifei HUANG ; Bin WU ; Xiaolong QI
Chinese Journal of Digestive Endoscopy 2024;41(1):43-51
Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
4.Status of anemia and its association with feeding patterns in infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture
Xiaolan MA ; Huiling WANG ; Ting CAO ; Xiaorong MA ; Juanjuan XU ; Qi HAN ; Haolan MA ; Xiaoyang HE ; Jianhua MA ; Gexiang ZHANG
Chinese Journal of Child Health Care 2024;32(3):273-279
【Objective】 To investigate the anemia status of infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture, Gansu Province, and to comprehensively evaluate the differences in feeding behaviors between anaemic and normal children through the infant and child feeding index (ICFI) and feeding knowledge scores, so as to provide reference for the guidance of infants and young children feeding in ethnic minority areas and the promotion of children′s growth and development. 【Methods】 Taking infants and young children aged 6 - 24 months in Linxia Prefecture as the study subjects, a multi-stage random sampling method was used to select children who met the requirements from 5 townships and 5 villages in 7 counties in 2019 and 2020.Periphral blood samples were collected to test the level of hemoglobin, so as to determine the anemia status.Meanwhile, physical examination was performed and a questionnaire survey of guardians was conducted to analyze the association betweenanaemia and feeding patterns 【Results】 A total of 3 901 infants and children were included in this study, of whom 729 (18.70%) were anaemic, with a mean ICFI score of 12.56±2.70 and a mean feeding knowledge score of 1.97±1.01.There was no statistically significant association of low feeding knowledge score and low ICFI with anaemia after adjusting for confounders (P>0.05), Unqualified meat addition in ICFI was a risk factor for anaemia (OR=1.355, P=0.042), while non-bottle feeding in the past 24 hours (OR=0.762, P=0.021), and breastfeeding in the past 24 hours of infants and toddlers aged 12 - 24 months (OR=0.228, P=0.018) were protective factor for anemia in infants and toddlers aged 12 - 24 months. 【Conclusions】 The average prevalence of anemia in infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture of Gansu Province is high, but the level of infant feeding and the level of feeding knowledge of caregivers are low.Early adherence to breastfeeding, timely addition of supplementary food, and more comsumpution of meat for children are conducive to preventing anemia.
5.Summary of best evidence for perioperative nutritional management in elderly patients with hip fracture
Fanghui DONG ; Sanlian HU ; Tangyu CHEN ; Zhiling CHEN ; Qi LIN ; Huiling YUE
Chinese Journal of Modern Nursing 2024;30(6):727-734
Objective:To summarize the relevant evidence of perioperative nutritional management for elderly patients with hip fractures, so as to provide scientific guidance for clinical nursing staff to implement nutritional management.Methods:Literature related to perioperative nutrition management of elderly patients with hip fracture were systematically searched from domestic and foreign guide websites, professional association websites, as well as UpToDate, PubMed, BMJ, Web of Science, Cochrane Library, Embase, CINAHL, Chinese Medical Journal Network, Wanfang Database, CNKI and other databases. The search period was from the establishment of the databases to February 15, 2023. Three researchers conducted quality evaluation and data extraction on the literature.Results:A total of 20 articles were included, including one clinical decision, six guidelines, seven expert consensus and six systematic reviews. After extracting and integrating the evidence included in the literature, a total of 29 best pieces of evidence were finally summarized from eight aspects, such as establishing a multidisciplinary nutrition support team, nutrition risk screening, nutrition assessment and content, nutrition support goals, nutrition support methods, preoperative and postoperative nutrition support, health education and follow-up.Conclusions:This study summarizes 29 best evidence for perioperative nutrition management in elderly patients with hip fractures. Nursing staff can develop scientific and standardized perioperative nutrition management plans for elderly patients with hip fracture based on clinical conditions, improving their nutritional status and clinical prognosis.
6.Diagnostic value of musculoskeletal ultrasound in patients with limb pain
Zhengxi LONG ; Bei FU ; Qi FAN ; Yan SONG ; Lihua LUO ; Tingting LIU ; Huiling QI ; Sujiang CHEN
China Modern Doctor 2024;62(13):8-10
Objective To explore the diagnostic value of musculoskeletal ultrasound in patients with limb pain.Methods A total of 80 patients with limb pain admitted to the First Hospital of Nanchang from January 2021 to December 2022 were included in the study.All patients received magnetic resonance imaging(MRI)and musculoskeletal ultrasound on admission.The consistency and coincidence rate of musculoskeletal ultrasound and MRI in diagnosing the cause of limb pain were compared.Results In the 80 patients,MRI and musculoskeletal ultrasound detected positive results in 78 cases,accounting for 97.50%,and 2 cases had no clear disease type.According to the results of MRI,there were 75 cases in which musculoskeletal ultrasound diagnosis of the cause of limb pain was consistent with the MRI results,and total coincidence rate was 96.15%(75/78),with excellent consistency(Kappa=0.907).Conclusion Musculoskeletal ultrasound can clearly display the fine tissue structure,and the diagnosis accuracy of limb pain is high,and the diagnosis consistency with MRI is excellent.
7.Effect of shared medical appointments on blood glucose levels and self-management behavior in patients with gestational diabetes mellitus
Wanying WANG ; Tingting HAN ; Xiaofan LU ; Chong XU ; Ying ZHANG ; Yalan QI ; Huaping YIN ; Huiling ZOU ; Yu SUN
Journal of Clinical Medicine in Practice 2024;28(16):109-113
Objective To investigate the impact of the Shared Medical Appointment (SMA) model on blood glucose levels and self-management behaviors in patients with gestational diabetes mellitus (GDM). Methods A total of 87 pregnant women diagnosed with GDM at the Obstetrics and Gynecology and Endocrinology Outpatient Departments of the Affiliated Suqian Hospital of Xuzhou Medical University from October 2021 to October 2022 were enrolled and divided into treatment group (
8.Effect of Tongdu Xingshen Needling Method (通督醒神针刺法) on Expression of AMPA Receptors and Their Accessory Proteins in the Hippocampus of Rats with Learning Memory Impairment After Cerebral Ischaemia-Reperfusion
Xiaodi RUAN ; Jing GAO ; Zhuan LYU ; Qi LI ; Kaiqi SU ; Yiming GU ; Mingyue YU ; Shikui QI ; Meng LUO ; Mingli WU ; Huiling WANG ; Xin SHEN ; Xiaodong FENG
Journal of Traditional Chinese Medicine 2023;64(23):2435-2442
ObjectiveTo explore the possible mechanism of Tongdu Xingshen needling method (通督醒神针刺法) on post-stroke cognitive impairment. MethodsSD rats were randomly divided into a normal group (n=12), a sham surgery group (n=12), a model group (n=12), and a electroacupuncture group (n=13). The rats in the model group and electroacupuncture group were subjected to the wire bolus method to establish the rats model with learning memory impairment after cerebral ischaemia-reperfusion. After successful modelling, the rats in the electroacupuncture group were given electroacupuncture interventions at “Shenting (GV 24)” and “Baihui (GV 20)” once a day for 30 minutes for 14 days. The other three groups did not receive other interventions but grasp. A 5-day localisation navigation experiment was conducted on the 9th day of intervention, and a spatial exploration experiment was conducted on the 14th day of intervention to evaluate the learning and memory abilities of the rats. After the spatial exploration experiment, hippocampal tissues were taken from each group of rats, and the changes in the volume of cerebral infarction were observed by TTC staining; the changes in the morphology of pyramidal neurons and the density of dendritic spines in the CA1 area of the hippocampus were observed by Golgi staining; protein immunoblotting was used to detect the relative protein expression of the subunits of the α-amino-3-carboxy-5-methylisoxazole-4-propionic acid (AMPA) receptor including glutamate receptor 1 (GluR1), glutamate receptor 2 (GluR2), glutamate receptor 3 (GluR3) and auxiliary proteins TARPγ2, TARPγ8 in hippocampal tissues of rats in each group; the real-time fluorescence quantitative PCR was used to detect GluR1, GluR2, GluR3 mRNA levels in the hippocampal tissues of rats. ResultsIn the localisation navigation experiment, compared with the normal group and sham surgery group, the escape latency and total distance of rats in the model group were significantly extended (P<0.05) at day 1, 2, 3, 4, and 5; and the escape latency and total distance of rats in the electroacupuncture group tended to be significantly shorter than those in the model group (P<0.05). In the spatial exploration experiment, compared with the normal group and the sham surgery group, the number of rats crossing the platform in the model group was significantly reduced (P<0.05), and the number of crossings of the platform in the electroacupuncture group increased significantly (P<0.05). The results of TTC staining showed that the volume of cerebral infarction increased clearly in the model group compared with the sham surgery group (P<0.05), and apparently decreased in the electroacupuncture group compared with the model group (P<0.05). Golgi staining showed that the number of dendritic branches of pyramidal neurons and dendritic spines in hippocampal CA1 region significantly decreased in the model group compared with the normal group and the sham surgery group (P<0.05). The number of dendritic branches of pyramidal neurons and the density of dendritic spines in hippocampal CA1 region significantly increased in the electroacupuncture group compared with the model group (P<0.05). The protein relative expression levels of GluR1, GluR2, GluR3, TARPγ2 and TARPγ8, and the mRNA levels of GluR1, GluR2 and GluR3 in hippocampus decreased in the model group compared with the normal group and the sham surgery group (P<0.05). The protein relative expression levels of GluR1, GluR2, GluR3, TARPγ2 and TARPγ8, and the mRNA levels of GluR1, GluR2 and GluR3 in hippocampus increased in the electroacupuncture group compared with model group (P<0.05). ConclusionThe Tongdu Xingshen needling method can improve learning memory impairment after cerebral ischaemia-reperfusion, which may be related to up-regulation of the expression of AMPA receptor and their auxiliary protein TARP, and promoting the synaptic plasticity of hippocampal tissues.
9.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
10.Alleviating experimental pulmonary hypertension via co-delivering FoxO1 stimulus and apoptosis activator to hyperproliferating pulmonary arteries.
Bingbing LI ; Chao TENG ; Huiling YU ; Xiaohong JIANG ; Xuyang XING ; Qi JIANG ; Chenshi LIN ; Zongmin ZHAO ; Ruifeng ZHANG ; Wei HE
Acta Pharmaceutica Sinica B 2023;13(6):2369-2382
Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.


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