1.Investigation of the Influence of Lipoprotein(a) and Oxidized Lipoprotein(a) on Plasminogen Activation and Fibrinolysis
Matthew YAO ; S. Kent DICKESON ; Karthik DHANABALAN ; Sergey SOLOMEVICH ; Connor DENNEWITZ ; David GAILANI ; Wen-Liang SONG
Journal of Lipid and Atherosclerosis 2025;14(2):229-235
Objective:
In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis.
Methods:
Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples.
Results:
Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis.
Conclusion
This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.
2.Investigation of the Influence of Lipoprotein(a) and Oxidized Lipoprotein(a) on Plasminogen Activation and Fibrinolysis
Matthew YAO ; S. Kent DICKESON ; Karthik DHANABALAN ; Sergey SOLOMEVICH ; Connor DENNEWITZ ; David GAILANI ; Wen-Liang SONG
Journal of Lipid and Atherosclerosis 2025;14(2):229-235
Objective:
In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis.
Methods:
Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples.
Results:
Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis.
Conclusion
This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.
3.Investigation of the Influence of Lipoprotein(a) and Oxidized Lipoprotein(a) on Plasminogen Activation and Fibrinolysis
Matthew YAO ; S. Kent DICKESON ; Karthik DHANABALAN ; Sergey SOLOMEVICH ; Connor DENNEWITZ ; David GAILANI ; Wen-Liang SONG
Journal of Lipid and Atherosclerosis 2025;14(2):229-235
Objective:
In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis.
Methods:
Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples.
Results:
Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis.
Conclusion
This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.
4.Return-to-work among COVID-19 survivors in the Philippines and the role of rehabilitation: A mixed-method design
Michael P. Sy ; Roi Charles S. Pineda ; Daryl Patrick G. Yao ; Hans D. Togonon ; Eric Asaba
Acta Medica Philippina 2025;59(Early Access 2025):1-12
BACKGROUND
A substantial number of COVID-19 recoverees are working-aged individuals, which makes return-towork (RTW) an essential part of rehabilitation. Many COVID-19 recoverees must deal with physical and mental symptoms of post-COVID conditions such as fatigue, dyspnea, difficulty concentrating, memory lapses, and anxiety. These symptoms coupled with often insufficient support from employers and the government can make the RTW process complicated. Although research related to RTW after COVID-19 has begun to emerge over the years, few primary studies have come out from developing countries.
OBJECTIVESThis exploratory study aims to describe perceived work ability and health-related quality of life, lived experiences of the RTW process, and role of rehabilitation in a limited sample of Filipino COVID-19 recoverees.
METHODSUsing purposive sampling and a convergent parallel mixed-method design, the study draws on an online survey and group interviews to understand expectations, experiences, and self-rated work ability of working-age adults with post-COVID condition. We report the findings of the questionnaire data using descriptive statistics. From the questionnaire respondents, eight participants were interviewed to explore the RTW experiences from multiple perspectives. The group interview was conducted online, and narrative analysis was used to explore the data. This analytic process involved an iterative and inductive process between data gathering and data analysis.
RESULTSFindings from our narrative analysis are reported under four themes: 1) The period of liminality; 2) A ‘positive’ problem; 3) Health as a psychosocial and justice issue; and 4) The reimagination of paid work. The narratives gathered document an overview of how selected Filipinos overcame the COVID-19 infection and their recovery and RTW process.
CONCLUSIONResults call for a re-examination of the concept of health and paid work for individuals undergoing rehabilitation and recovery.
Human ; Pandemics ; Rehabilitation, Vocational ; Occupational Therapy
5.Investigation of the Influence of Lipoprotein(a) and Oxidized Lipoprotein(a) on Plasminogen Activation and Fibrinolysis
Matthew YAO ; S. Kent DICKESON ; Karthik DHANABALAN ; Sergey SOLOMEVICH ; Connor DENNEWITZ ; David GAILANI ; Wen-Liang SONG
Journal of Lipid and Atherosclerosis 2025;14(2):229-235
Objective:
In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis.
Methods:
Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples.
Results:
Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis.
Conclusion
This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.
6.Return-to-work among COVID-19 survivors in the Philippines and the role of rehabilitation: A mixed-method design.
Michael P. SY ; Roi Charles S. PINEDA ; Daryl Patrick G. YAO ; Hans D. TOGONON ; Eric ASABA
Acta Medica Philippina 2025;59(20):60-71
BACKGROUND
A substantial number of COVID-19 recoverees are working-aged individuals, which makes return-towork (RTW) an essential part of rehabilitation. Many COVID-19 recoverees must deal with physical and mental symptoms of post-COVID conditions such as fatigue, dyspnea, difficulty concentrating, memory lapses, and anxiety. These symptoms coupled with often insufficient support from employers and the government can make the RTW process complicated. Although research related to RTW after COVID-19 has begun to emerge over the years, few primary studies have come out from developing countries.
OBJECTIVESThis exploratory study aims to describe perceived work ability and health-related quality of life, lived experiences of the RTW process, and role of rehabilitation in a limited sample of Filipino COVID-19 recoverees.
METHODSUsing purposive sampling and a convergent parallel mixed-method design, the study draws on an online survey and group interviews to understand expectations, experiences, and self-rated work ability of working-age adults with post-COVID condition. We report the findings of the questionnaire data using descriptive statistics. From the questionnaire respondents, eight participants were interviewed to explore the RTW experiences from multiple perspectives. The group interview was conducted online, and narrative analysis was used to explore the data. This analytic process involved an iterative and inductive process between data gathering and data analysis.
RESULTSFindings from our narrative analysis are reported under four themes: 1) The period of liminality; 2) A ‘positive’ problem; 3) Health as a psychosocial and justice issue; and 4) The reimagination of paid work. The narratives gathered document an overview of how selected Filipinos overcame the COVID-19 infection and their recovery and RTW process.
CONCLUSIONResults call for a re-examination of the concept of health and paid work for individuals undergoing rehabilitation and recovery.
Human ; Pandemics ; Rehabilitation, Vocational ; Occupational Therapy
7.Study on the role and mechanism of SDC2 expression in regulating ferroptosis and cervical cancer
Xueqin Yao ; Xuelian Xiao ; Qiying Luo ; Deping Chang ; Yan Gao
Acta Universitatis Medicinalis Anhui 2025;60(2):234-239
Objective:
To investigate whether syndecan-2(SDC2) can affect the proliferation, invasion and migration of cervical cancer cells by regulating ferroptosis and its possible mechanism.
Methods :
Normal cervical epithelial cells H8 and cervical squamous carcinoma cells C33A were cultured and divided into H8 group and C33A group. C33A cells were cultured and divided into control group, low SDC2 expression group, SDC2+ferroptosis inhibitor(ferrostation-1) group and SDC2 + ferroptosis inducer(erastin) group. Western blot was used to detect the protein levels of SDC2, solute carrier family 7 member 11(SLC7A11) and glutathione peroxidase 4(GPX4). RT-qPCR was used to detect the SDC2 mRNA level in C33A cells. ELISA kits were used to detect the levels of reactive oxygen species(ROS), glutathione(GSH) and ferrous ion(Fe2+) in C33A cells. The cloning ability of C33A cells was detected by plate cloning. The migration ability of C33A cells was detected by scratch test. Transwell assay was used to detect the invasion ability of C33A cells.
Results :
Compared with H8 group, the protein and mRNA expressions of SDC2, SLC7A11 and GPX4 in C33A group increased(P<0.05). Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells in the low SDC2 group decreased(P<0.05), the protein and mRNA expressions of SLC7A11 and GPX4 in C33A cells decreased(P<0.05), and the GSH level decreased. ROS and Fe2+levels increased(P<0.05). Compared with the low SDC2 group, the protein and mRNA expressions of SLC7A11 and GPX4 increased(P<0.05), the GSH level increased, and the ROS and Fe2+levels decreased(P<0.05) in the low SDC2+ferrostation-1 group. Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells with low SDC2+erastin expression decreased(P<0.05).
Conclusion
The expression of SDC2 increases in C33A cervical cancer cells. Low expression of SDC2 can activate SLC7A11/GPX4 pathway mediated ferroptosis, thereby reducing the proliferation, invasion and migration of C33A cells.
8.Andrographolide reduces cisplatin resistance of endometrial cancer Ishikawa/DPP cells by inhibiting the Fas/FasL signaling axis
YAO Suhuan1 ; SHI Lifeng1 ; LI Shufang2, ; DONG Suxia2 ; CHEN Ping3
Chinese Journal of Cancer Biotherapy 2024;32(2):154-160
目的:探讨穿心莲内酯(Andro)调节脂肪酸合成酶(Fas)/脂肪酸合成酶配体(FasL)信号轴对子宫内膜癌Ishikawa细胞顺铂(DDP)耐药性的影响。方法:采用0、5、10、20 μg/mL DDP分别处理Ishikawa细胞和顺铂耐药的Ishikawa/DPP细胞,0、5、10、25、50 μmol/L Andro处理Ishikawa/DDP细胞,MTT法检测细胞增殖情况并为后续实验选择合适的给药剂量。将Ishikawa/DDP细胞随机分为对照组、DDP组(DDP干预)、Andro组(DDP、Andro干预)、pcDNA3.1-NC组(转染pcDNA3.1+DDP、Andro干预)、pcDNA3.1-Fas/FasL组(转染pcDNA3.1-Fas/FasL+DDP、Andro干预),24 h后,采用qPCR法检测Fas、FasL mRNA的表达,平板克隆形成实验、Transwell实验和流式细胞术分别检测细胞克隆能力、细胞迁移与侵袭和细胞凋亡,WB法检测增殖细胞核抗原(PCNA)、BAX、Bcl-2、MMP-2、PD-L1、多药耐药蛋白-1(MDR-1)及Fas、FasL蛋白表达。结果:DDP以剂量依赖的方式抑制Ishikawa和Ishikawa/DPP细胞增殖,并且与Ishikawa细胞比较,Ishikawa/DPP细胞对DDP的敏感性更低(均P<0.05);Andro以剂量依赖性的方式抑制Ishikawa/DPP细胞的增殖(均P<0.05)。Ishikawa/DPP细胞中Fas、FasL的表达水平均高于Ishikawa细胞(均P<0.05)。选取20 μg/mL DDP和25 μmol/L Andro为干预剂量,干预时间24 h。与对照组比较,DDP组Ishikawa/DPP细胞中PD-L1、MDR-1、Fas、FasL mRNA及蛋白表达水平显著升高(P<0.05),而克隆形成率、迁移与侵袭细胞数、凋亡率差异均无统计学意义(均P>0.05);与DDP组比较,Andro组Ishikawa/DPP细胞中Fas、FasL mRNA表达水平、细胞克隆形成率、迁移与侵袭细胞数、PCNA、Bcl-2、MMP-2、PD-L1、MDR-1、Fas、FasL蛋白表达水平显著降低,BAX蛋白表达水平及凋亡率显著升高(P<0.05或P<0.01),pcDNA3.1-NC组与Andro组类似;与pcDNA3.1-NC组比较,pcDNA3.1-Fas/FasL组Ishikawa/DPP细胞上述指标变化均被逆转(P<0.05)。结论:Andro可能通过抑制Fas/FasL信号轴来抑制Ishikawa/DPP细胞增殖、迁移与侵袭,促进凋亡,从而降低细胞对DDP的耐药性。
9.Exploration of CT imaging features of cystic pulmonary nodules and establishment of a prediction model for benign and malignant pulmonary nodules
Yi YAO ; Qiuxia HU ; Yanhui YANG ; Xiaoyang XIE ; Yi WANG ; Xiaoliang LI ; Lei LUO ; Ji LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):249-254
Objective To explore the CT imaging features and independent risk factors for cystic pulmonary nodules and establish a malignant probability prediction model. Methods The patients with cystic pulmonary nodules admitted to the Department of Thoracic Surgery of the First People's Hospital of Neijiang from January 2017 to February 2022 were retrospectively enrolled. They were divided into a malignant group and a benign group according to the pathological results. The clinical data and preoperative chest CT imaging features of the two groups were collected, and the independent risk factors for malignant cystic pulmonary nodules were screened out by logistic regression analysis, so as to establish a prediction model for benign and malignant cystic pulmonary nodules. Results A total of 107 patients were enrolled. There were 76 patients in the malignant group, including 36 males and 40 females, with an average age of 59.65±11.74 years. There were 31 patients in the benign group, including 16 males and 15 females, with an average age of 58.96±13.91 years. Multivariate logistic analysis showed that the special CT imaging features such as cystic wall nodules [OR=3.538, 95%CI (1.231, 10.164), P=0.019], short burrs [OR=4.106, 95%CI (1.454, 11.598), P=0.008], cystic wall morphology [OR=6.978, 95%CI (2.374, 20.505), P<0.001], and the number of cysts [OR=4.179, 95%CI (1.438, 12.146), P=0.009] were independent risk factors for cystic lung cancer. A prediction model was established: P=ex/(1+ex), X=–2.453+1.264×cystic wall nodules+1.412×short burrs+1.943×cystic wall morphology+1.430×the number of cysts. The area under the receiver operating charateristic curve was 0.830, the sensitivity was 82.9%, and the specificity was 74.2%. Conclusion Cystic wall nodules, short burrs, cystic wall morphology, and the number of cysts are the independent risk factors for cystic lung cancer, and the established prediction model can be used as a screening method for cystic pulmonary nodules.
10.Application of alpha-fetoprotein and IL-6 in prognostic prediction of patients with hepatitis B related liver failure
Journal of Public Health and Preventive Medicine 2024;35(3):141-144
Objective To analyze the application value of alpha-fetoprotein (AFP) and interleukin-6 (IL-6) in prognosis prediction of hepatitis B virus (HBV) associated liver failure. Methods A total of 135 patients with HBV-related liver failure who underwent treatment at the Infection Department of the Second People's Hospital of Yibin City from July 2020 to June 2022 were selected as the study subjects (observation group). Additionally, 100 patients who underwent physical examination in the hospital during the same period with normal indicators were selected as the control group. Serum levels of AFP and IL-6 were compared between the two groups. Factors influencing the prognosis of HBV-related liver failure were analyzed. Multiple logistic regression was used to analyze the risk factors affecting the prognosis of HBV-related liver failure patients. Results The levels of serum AFP and IL-6 in the control group were lower than those in the control group, and the difference was statistically significant (P<0.05). The two groups showed statistically significant differences in clinical symptoms such as hepatic encephalopathy, hepatorenal syndrome, ascites, and disease type (P<0.05). Multiple logistic regression analysis showed that the clinical symptoms of hepatic encephalopathy, hepatorenal syndrome, ascites and AFP≥25 μg/L and IL-6>10.0 pg/mL were risk factors affecting the prognosis of HBV-related liver failure. Conclusion Serum AFP and IL-6 can predict the prognosis of patients with HBV-related liver failure, which is worthy of clinical study.


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