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1.
J Mol Med (Berl) ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727748

ABSTRACT

Atherosclerosis (AS) is a chronic inflammatory vascular disease that occurs in the intima of large and medium-sized arteries with the immune system's involvement. It is a common pathological basis for high morbidity and mortality of cardiovascular diseases. Abnormal proliferation of apoptotic cells and necrotic cells leads to AS plaque expansion, necrotic core formation, and rupture. In the early stage of AS, macrophages exert an efferocytosis effect to engulf and degrade apoptotic, dead, damaged, or senescent cells by efferocytosis, thus enabling the regulation of the organism. In the early stage of AS, macrophages rely on this effect to slow down the process of AS. However, in the advanced stage of AS, the efferocytosis of macrophages within the plaque is impaired, which leads to the inability of macrophages to promptly remove the apoptotic cells (ACs) from the organism promptly, causing exacerbation of AS. Moreover, upregulation of CD47 expression in AS plaques also protects ACs from phagocytosis by macrophages, resulting in a large amount of residual ACs in the plaque, further expanding the necrotic core. In this review, we discussed the molecular mechanisms involved in the process of efferocytosis and how efferocytosis is impaired and regulated during AS, hoping to provide new insights for treating AS.

2.
BMC Public Health ; 24(1): 1181, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671417

ABSTRACT

BACKGROUND: In China, the world's largest developing country, low back pain (LBP) is a common public health issue affecting workability. This meta-analysis aimed to systematically assess the risk factors of LBP in the Chinese population. METHODS: Four English language and four Chinese databases were searched, and cross-sectional studies on the risk factors for LBP in Chinese populations were identified and collected. The search timeframe covered the period from the establishment of the database to November 2023. Two researchers independently reviewed the literature, extracted the data, and evaluated the risk of bias. Begg's and Egger's tests were used to evaluate publication bias. RESULTS: Fifteen cross-sectional studies involving 86,575 people were included. Seven risk factors for LBP were identified. Six risk factors were statistically significant: Cigarette smoking (odds ratio [OR] = 1.55; 95% confidence interval [CI]: 1.15, 2.08, P = 0.004, I2 = 72%), body mass index (BMI) ≥ 28 kg/m² (OR = 4.51; 95% CI: 3.36, 6.07, P < 0.00001, I2 = 8%), female sex (OR = 1.54; 95% CI: 1.25, 1.90, P < 0.0001, I2 = 63%), vibration exposure at work (OR = 1.65; 95% CI: 1.16, 2.34, P = 0.006, I2 = 84%), working overtime (OR = 2.57; 95% CI: 1.12, 5.91, P = 0.03, I2 = 85%), and lack of exercise (OR = 2.48; 95% CI: 1.62, 3.78, P < 0.0001, I2 = 0%). One risk factor that was not statistically significant was standing for long periods (OR = 1.02; 95% CI: 0.82, 1.26, P = 0.88, I2 = 73%). CONCLUSIONS: This study found that smoking, a BMI ≥ 28 kg/m², female sex, vibration exposure at work, working overtime, and lack of exercise may be risk factors for LBP in the Chinese population. Because the included studies were cross-sectional and the certainty of the evidence was very low, the results need to be interpreted cautiously. Multicentre, high-quality studies should be conducted in the future. To reduce the prevalence of LBP, the Chinese government and hospitals must develop early screening programs and implement effective preventive and interventional measures. TRIAL REGISTRATION: This study is registered in the PROSPERO database (No. CRD42023447857).


Subject(s)
Low Back Pain , Humans , Low Back Pain/epidemiology , Risk Factors , China/epidemiology , Cross-Sectional Studies , Female , Body Mass Index , Male
3.
Mini Rev Med Chem ; 24(4): 391-402, 2024.
Article in English | MEDLINE | ID: mdl-37259932

ABSTRACT

Canopy FGF signaling regulator 2 (CNPY2) is a novel angiogenic growth factor. In recent years, increasing evidence highlights that CNPY2 has important functions in health and disease. Many new blood vessels need to be formed to meet the nutrient supply in the process of tumor growth. CNPY2 can participate in the development of tumors by promoting angiogenesis. CNPY2 also enhances neurite outgrowth in neurologic diseases and promotes cell proliferation and tissue repair, thereby improving cardiac function in cardiovascular diseases. Regrettably, there are few studies on CNPY2 in various diseases. At the same time, its biological function and molecular mechanism in the process and development of disease are still unclear. This paper reviews the recent studies on CNPY2 in cervical cancer, renal cell carcinoma, prostate cancer, colorectal cancer, lung cancer, gastric cancer, hepatocellular carcinoma, cerebral ischemia-reperfusion injury, spinal cord ischemia-reperfusion injury, Parkinson's disease, ischemic heart disease, myocardial ischemiareperfusion injury, myocardial infarction, heart failure, and non-alcoholic fatty liver disease. The biological function and molecular mechanism of CNPY2 in these diseases have been summarized in this paper. Many drugs that play protective roles in tumors, cardiovascular diseases, non-alcoholic fatty liver disease, and neurologic diseases by targeting CNPY2, have also been summarized in this paper. In addition, the paper also details the biological functions and roles of canopy FGF signaling regulator 1 (CNPY1), canopy FGF signaling regulator 3 (CNPY3), canopy FGF signaling regulator 4 (CNPY4), and canopy FGF signaling regulator 5 (CNPY5). The mechanism and function of CNPY2 should be continued to study in order to accelerate disease prevention in the future.


Subject(s)
Cardiovascular Diseases , Liver Neoplasms , Lung Neoplasms , Non-alcoholic Fatty Liver Disease , Reperfusion Injury , Male , Humans , Adaptor Proteins, Signal Transducing/metabolism , Lung Neoplasms/pathology
4.
Int J Biol Macromol ; 254(Pt 1): 127517, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37865355

ABSTRACT

This study presents a novel approach in which a dual network (DN) composite, comprising polyvinyl alcohol (PVA) and ribbon-like nanocellulose (RC), was synthesized in one step using the volume exclusion effect involved in enzyme-catalyzed cellulose synthesis. Additionally, the impact of PVA as a crowding reagent during enzymatic catalysis on the in situ formation of nanocellulose and its resulting aspect ratio was explored. In contrast, the other two composites were created by incorporating enzyme-catalyzed synthetic block cellulose (BC) and its acid-hydrolyzed regenerated disc-shaped cellulose (DC) into the PVA. Subsequently, the mechanism by which three distinct types of nanocellulose, varying in morphology and size, was explored to elucidate their contributions to enhancing the properties of PVA. The results demonstrated that PVA/RC outperformed PVA/BC and PVA/DC. The elevated aspect ratio and intricate network structure of RCs not only significantly bolster the mechanical robustness of PVA/RC, leading in an 86.40 % surge in tensile strength and a remarkable 277.03 % rise in tensile modulus in comparison to pure PVA, but also induce a slight enhancement in elongation at break. Moreover, the thermal stability and biodegradability of PVA/RC was enhanced. Collectively, this study introduces an innovative strategy for the efficient fabrication of biodegradable composites with enhanced properties.


Subject(s)
Cellulose , Polyvinyl Alcohol , Polyvinyl Alcohol/chemistry , Tensile Strength , Cellulose/chemistry
5.
J Orthop Surg Res ; 18(1): 727, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37752526

ABSTRACT

BACKGROUND: Vibration therapy (VT), a treatment of musculoskeletal disorders, has been developed for clinical applications in the past decade. However, its effect on relieving chronic low back pain (CLBP) and improving lumbar function is still illusive, lacking sufficient evidence-based medical data. OBJECTIVE: This systematic review aimed to evaluate the efficacy of vibration therapy on pain and function in people with CLBP. METHODS: PubMed, Cochrane Library, Web of Science, Embase, CNKI, Wanfang Date, VIP, and CBM were applied to search for clinical randomized controlled trials (RCTs) on vibration therapy for people with CLBP. The electronic databases were searched from the establishment of the database until July 1, 2023. Two researchers assessed the quality of the included studies and extracted data. The outcome indicators included the pain intensity index, Oswestry dysfunction index (ODI) score, and Roland-Morris dysfunction questionnaire (RMDQ) score. GRADE was used to evaluate the certainty of evidence of each outcome indicator. The meta-analysis was conducted using RevMan 5.3 software. RESULTS: Fourteen papers met the inclusion criteria with 860 subjects (VT group n = 432 and control group n = 428). VT for patients with CLBP reduced the pain intensity index [SMD = - 0.71, 95% CI (- 1.02, - 0.39), I2 = 76%, P < 0.0001], the ODI score value [MD = - 4.24, 95% CI (- 8.10, - 0.38), I2 = 88%, P = 0.03], and the RMDQ score value [MD = - 2.21, 95% CI (- 3.41, - 1.01), I2 = 0%, P = 0.0003]. Subgroup analysis displayed that the pain intensity index was lower in the whole-body vibration (WBV) group than in the control group [SMD = - 0.49, 95% CI (- 0.79, - 0.19), I2 = 58%, P = 0.001] and the local vibration (LV) group [SMD = - 1.07, 95% CI (- 1.60, - 0.53), I2 = 76%, P < 0.0001]. The ODI scores in the WBV group were lower than those in the control group [MD = - 3.30, 95% CI (- 5.76, - 0.83), I2 = 36%, P = 0.009]. There was no statistically significant difference in ODI scores between the LV group and the control group [MD = - 5.78, 95% CI (- 16.23, 4.66), I2 = 97%, P = 0.28]. CONCLUSION: The data from this study suggest that VT can reduce pain and improve lumbar function in patients with CLBP. However, we still need to carefully interpret the results of this study, as the certainty of evidence was low, and the clinical relevance of the results is questionable. Further RCTs are needed in the future to ascertain this.


Subject(s)
Chronic Pain , Low Back Pain , Musculoskeletal Diseases , Humans , Low Back Pain/therapy , Vibration/therapeutic use , Physical Therapy Modalities , Pain Measurement , Chronic Pain/therapy
6.
Mini Rev Med Chem ; 23(19): 1905-1911, 2023.
Article in English | MEDLINE | ID: mdl-36967462

ABSTRACT

With the development of the social economy over the last 30 years, non-alcoholic fatty liver disease (NAFLD) is affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. It is very important to investigate the pathogenesis and treatment of NAFLD for the development of human health. Probucol is an antioxidant with a bis-phenol structure. Although probucol is a clinically used cholesterol-lowering and antiatherosclerosis drug, its mechanism has not been elucidated in detail. This paper reviews the chemical structure, pharmacokinetics and pharmacological research of probucol. Meanwhile, this paper reviews the mechanism of probucol in NAFLD. We also analyzed and summarized the experimental models and clinical trials of probucol in NAFLD. Although current therapeutic strategies for NAFLD are not effective, we hope that through further research on probucol, we will be able to find suitable treatments to solve this problem in the future.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Probucol/pharmacology , Probucol/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Cholesterol/pharmacology , Liver
7.
Int Immunopharmacol ; 118: 110013, 2023 May.
Article in English | MEDLINE | ID: mdl-36931172

ABSTRACT

With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. As a chronic liver disease, NAFLD is deeply affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. As a protein complex in clinical research, the inflammasomes play a crucial role in the development of NAFLD, atherosclerosis, and other diseases. This paper reviews the types, composition, characteristics of inflammasomes, and molecular mechanism of the inflammasome in NAFLD. Meanwhile, the paper reviews the drugs and non-drugs that target NLRP3 inflammasome in the treatment of NAFLD in the past decades. we also analyzed and summarized the related experimental models, mechanisms, and results of NAFLD. Although current therapeutic strategies for NAFLD are not effective, we expect that we will be able to find an appropriate treatment to address this problem in the future with further research on inflammasome.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Liver/metabolism
8.
Anticancer Drugs ; 34(9): 995-1001, 2023 10 01.
Article in English | MEDLINE | ID: mdl-36728989

ABSTRACT

Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.


Subject(s)
Neoplasms , Protein Serine-Threonine Kinases , Humans , Protein Serine-Threonine Kinases/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Signal Transduction , Glucose/metabolism , Inflammation , Neoplasms/drug therapy
9.
J Pharm Pharmacol ; 75(3): 363-369, 2023 Mar 12.
Article in English | MEDLINE | ID: mdl-36508340

ABSTRACT

Salusins are discovered in 2003 and divided into salusin-α and salusin-ß, which are bioactive peptides with hemodynamic and mitotic activity and mainly distributed in plasma, urine, endocrine glands and kidneys. A large number of studies have shown that salusins can regulate lipid metabolism, inflammatory response and vascular proliferation. Despite the profound and diverse physiological properties of salusins, the exact mechanism of their cardiovascular effects remains to be determined. The potential mechanisms of action of salusins in cardiovascular-related diseases such as atherosclerosis, hypertension, heart failure, myocardial infarction and myocarditis, and their use as biomarkers of cardiovascular disease are discussed. This review aims to provide a new strategy for the diagnosis and prevention of clinical cardiovascular diseases.


Subject(s)
Cardiovascular Diseases , Myocardial Infarction , Humans , Intercellular Signaling Peptides and Proteins , Heart , Peptides
10.
Int J Biol Macromol ; 225: 776-785, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36403771

ABSTRACT

Biodegradable materials with antibacterial properties are highly promising. A novel antimicrobial nanocellulose (ECP) was synthesized in one-step by enzyme-catalyzed method to improve the mechanical and antimicrobial properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(HB-co-HV)]. The biodegradable nanocomposites were prepared by melt blending and the performance analysis results show that the nanocomposites display enhanced mechanical performances and antibacterial activities. Compared with the neat P(HB-co-HV), the P(HB-co-HV) doped with 0.5 wt%-ECP shows the highest mechanical properties with yield strength/elongation at break of 29.3 MPa, 7.63 %, respectively, an increase of 38 %/59 %, and a clear inhibition zone against Staphylococcus aureus (S. aureus) of approximately 3.0 mm. As a heterogeneous nucleation agent, ECP optimizes nucleation, and the interfacial interaction between phenol group and matrix promotes the compatibility and dispersion of ECP, resulting in superior mechanical properties of ECP-based composites. The P(HB-co-HV)/ECP nanocomposites have great potential in biomedical materials especially for the bone defect filling material.


Subject(s)
Anti-Infective Agents , Cellulose , 3-Hydroxybutyric Acid , Polyesters/pharmacology , Staphylococcus aureus , Hydroxybutyrates , Anti-Bacterial Agents/pharmacology
11.
Adv Mater ; 35(1): e2207587, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36284475

ABSTRACT

With the strengthening capacity through harnessing multi-length-scale structural hierarchy, synthetic hydrogels hold tremendous promise as a low-cost and abundant material for applications demanding unprecedented mechanical robustness. However, integrating high impact resistance and high water content, yet superior softness, in a single hydrogel material still remains a grand challenge. Here, a simple, yet effective, strategy involving bidirectional freeze-casting and compression-annealing is reported, leading to a hierarchically structured hydrogel material. Rational engineering of the distinct 2D lamellar structures, well-defined nanocrystalline domains and robust interfacial interaction among the lamellae, synergistically contributes to a record-high ballistic energy absorption capability (i.e., 2.1 kJ m-1 ), without sacrificing their high water content (i.e., 85 wt%) and superior softness. Together with its low-cost and extraordinary energy dissipation capacity, the hydrogel materials present a durable alternative to conventional hydrogel materials for armor-like protection circumstances.

12.
Article in Chinese | MEDLINE | ID: mdl-35634668

ABSTRACT

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups(n=8):model control group(MC),high frequency vibration group 1 (GP1,60 Hz),high frequency vibration 2 group (GP2,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1st,4 th and 7th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2~5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher (P<0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower(P<0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower (P<0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly (P<0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower (P<0.05 or P<0.01). But the expressions of Sox9 mRNA and protein were significantly higher (P< 0.05 or P<0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.


Subject(s)
Cartilage, Articular , Osteoarthritis, Knee , Animals , Cartilage, Articular/metabolism , MAP Kinase Kinase 4 , Male , NF-kappa B/metabolism , Osteoarthritis, Knee/therapy , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , SOX9 Transcription Factor , Vibration
13.
ACS Appl Mater Interfaces ; 14(15): 17826-17836, 2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35380790

ABSTRACT

In recent years, natural disasters such as hurricanes and floods have become more frequent, which usually leads to the pollution of drinking water. Drinking contaminated water may cause public health emergencies. The demand for healthy drinking water in disaster-affected areas is huge and urgent. Therefore, it is necessary to develop a simple water treatment technology suitable for emergencies. Inspired by nature, a fractional spray method was used to prepare graded purification material under mild conditions. The material consists of a calcium alginate isolation layer and a functional layer composed of calcium alginate, polyethylenimine, and water-based polyurethane, which can purify complex pollutants in water such as heavy metals, oils, pathogens, and micro/nano plastics through percolation. It does not require additional energy and can purify polluted water only under gravity. A disposable paper cup model was also designed, which can be used to obtain purified water by immersing in polluted water directly without other filtering devices. The test report shows that the water obtained from the paper cup was deeply purified. This design makes the material user-friendly and has the potential as a strategic material. This discovery can effectively improve the safety of drinking water after disasters and improve people's quality of life.


Subject(s)
Drinking Water , Water Purification , Alginates , Emergencies , Humans , Polyethyleneimine , Polyurethanes , Quality of Life
14.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(1): 42-46, 2022 Jan 30.
Article in Chinese | MEDLINE | ID: mdl-35150106

ABSTRACT

Based on the biomechanical mechanism of human upper limb, the disadvantages of traditional rehabilitation training and the current status of upper limb rehabilitation robot, a six degree of freedom, flexible adjustment, wearable upper limb rehabilitation exoskeleton design scheme is proposed. Firstly, the mechanics of each joint of the upper limb is analyzed, and the virtual prototype design of the whole mechanical structure of the upper limb rehabilitation wearable exoskeleton is carried out by using CATIA three-dimensional software. The tooth transmission of the forearm and the upper arm single row four point contact ball bearing with internal/external rotation and the shoulder flexible passive adjustment mechanism (viscoelastic damper) are innovatively designed. Then, the joints of the upper limb rehabilitation exoskeleton are analyzed, theoretical analysis and calculation of the driving torque, the selection of the motor and gearbox of each driving joint are carried out. Finally, the whole finite element analysis of the upper limb exoskeleton is carried out. The research and experimental results showed that the design scheme of the upper limb exoskeleton assist structure is highly feasible, which can help the patients with upper limb paralysis and motor dysfunction self-rehabilitation.


Subject(s)
Exoskeleton Device , Robotics , Stroke Rehabilitation , Wearable Electronic Devices , Biomechanical Phenomena , Humans , Torque , Upper Extremity
15.
Zhongguo Zhen Jiu ; 42(1): 59-65, 2022 Jan 12.
Article in Chinese | MEDLINE | ID: mdl-35025159

ABSTRACT

OBJECTIVE: To observe the effect of needle knife on chondrocyte autophagy and expressions of autophagy-related protein and mammalian target of rapamycin (mTOR) in rats with knee osteoarthritis (KOA), and to explore the possible mechanism of needle knife for KOA. METHODS: A total of 42 SD rats were randomly divided into a normal group, a model group and a needle knife group, 14 rats in each group. Except for the normal group, the other two groups were injected with the mixture of papain and L-cysteine into the left hind knee joint to establish the KOA model. After modeling, the rats in the needle knife group were treated with needle knife at strip or nodule around the quadriceps femoris and medial and lateral collateral ligament on the affected side, once a week for 3 times (3 weeks). The changes of left knee circumference in each group were observed; the chondrocytes and ultrastructure of left knee joint were observed by HE staining and electron microscope; the mRNA and protein expressions of autophagy-related genes (Atg5, Atg12, Atg4a), Unc-51 like autophagy activated kinase 1 (ULK1), autophagy gene Beclin-1 and mTOR in left knee cartilage were detected by real-time fluorescence quantitative PCR and Western blot. RESULTS: After modeling, the left knee circumferences in the model group and the needle knife group were increased compared with those before modeling and in the normal group (P<0.05); after intervention, the left knee circumference in the needle knife group was smaller than that in the model group and after modeling (P<0.05). Compared with the normal group, the number of chondrocytes was decreased, and a few cells swelled, nuclei shrank, mitochondria swelled and autophagosomes decreased in the model group; compared with the model group, the number of chondrocytes was increased , and most cell structures returned to normal, and autophagosomes was increased. Compared with the normal group, the mRNA and protein expressions of Atg5, Atg12, Atg4a, Beclin-1 and ULK1 in the knee cartilage in the model group were decreased (P<0.05); compared with the model group, the expressions of the above indexes in the needle knife group were increased (P<0.05). Compared with the normal group, the mRNA and protein expressions of mTOR in the knee cartilage in the model group were increased (P<0.05); compared with the model group, the expressions of the above indexes in the needle knife group were decreased (P<0.05). CONCLUSION: The needle knife intervention could improve knee cartilage injury in rats with KOA, and its mechanism may be related to reducing the expression of mTOR and up-regulating the expressions of Atg5, Atg12, Atg4a, ULK1 and Beclin-1, so as to promote chondrocyte autophagy and delay the aging and degeneration of chondrocytes.


Subject(s)
Osteoarthritis, Knee , Animals , Autophagy , Autophagy-Related Protein-1 Homolog/genetics , Beclin-1/genetics , Chondrocytes , Osteoarthritis, Knee/genetics , Osteoarthritis, Knee/therapy , Rats , Rats, Sprague-Dawley , TOR Serine-Threonine Kinases/genetics
17.
Sci Rep ; 12(1): 400, 2022 01 10.
Article in English | MEDLINE | ID: mdl-35013379

ABSTRACT

Fibroblast growth factor-21 (FGF-21) performs a wide range of biological functions in organisms. Here, we report for the first time that FGF-21 suppresses thrombus formation with no notable risk of bleeding. Prophylactic and therapeutic administration of FGF-21 significantly improved the degree of vascular stenosis and reduced the thrombus area, volume and burden. We determined the antithrombotic mechanism of FGF-21, demonstrating that FGF-21 exhibits an anticoagulant effect by inhibiting the expression and activity of factor VII (FVII). FGF-21 exerts an antiplatelet effect by inhibiting platelet activation. FGF-21 enhances fibrinolysis by promoting tissue plasminogen activator (tPA) expression and activation, while inhibiting plasminogen activator inhibitor 1 (PAI-1) expression and activation. We further found that FGF-21 mediated the expression and activation of tPA and PAI-1 by regulating the ERK1/2 and TGF-ß/Smad2 pathways, respectively. In addition, we found that FGF-21 inhibits the expression of inflammatory factors in thrombosis by regulating the NF-κB pathway.


Subject(s)
Blood Coagulation/drug effects , Fibrinolytic Agents/pharmacology , Fibroblast Growth Factors/pharmacology , Thrombosis/prevention & control , Animals , Blood Platelets/drug effects , Blood Platelets/metabolism , Cell Line , Cytokines/metabolism , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/metabolism , Factor VII/genetics , Factor VII/metabolism , Fibrinolysis/drug effects , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Humans , Male , Mice, Inbred ICR , NF-kappa B/metabolism , Plasminogen Activator Inhibitor 1/genetics , Plasminogen Activator Inhibitor 1/metabolism , Platelet Activation/drug effects , Rabbits , Signal Transduction , Smad2 Protein/metabolism , Thrombosis/blood , Thrombosis/genetics , Tissue Plasminogen Activator/genetics , Tissue Plasminogen Activator/metabolism , Transforming Growth Factor beta/metabolism
18.
J Cell Physiol ; 237(1): 86-97, 2022 01.
Article in English | MEDLINE | ID: mdl-34289095

ABSTRACT

Microtubule affinity regulating kinase 4 (MARK4), an important member of the serine/threonine kinase family, regulates the phosphorylation of microtubule-associated proteins and thus modulates microtubule dynamics. In human atherosclerotic lesions, the expression of MARK4 is significantly increased. Recently, accumulating evidence suggests that MARK4 exerts a proatherogenic effect via regulation of lipid metabolism (cholesterol, fatty acid, and triglyceride), inflammation, cell cycle progression and proliferation, insulin signaling, and glucose homeostasis, white adipocyte browning, and oxidative stress. In this review, we summarize the latest findings regarding the role of MARK4 in the pathogenesis of atherosclerosis to provide a rationale for future investigation and therapeutic intervention.


Subject(s)
Atherosclerosis , Protein Serine-Threonine Kinases , Atherosclerosis/genetics , Atherosclerosis/metabolism , Humans , Microtubules/metabolism , Phosphorylation , Signal Transduction
19.
ACS Omega ; 6(43): 29254-29266, 2021 Nov 02.
Article in English | MEDLINE | ID: mdl-34746613

ABSTRACT

The structural evolution of polyglycolide (PGA) and poly(glycolide-co-lactide) (P(GA-co-LA)) with 8% LA content fibers with different heat-setting temperatures was investigated during in vitro degradation using WAXD, SAXS, and mechanical property tests. It was found that the PGA fiber was more susceptible to the degradation process than the P(GA-co-LA) fiber and a higher heat-setting temperature reduced the degradation rate of the two samples. The weight and mechanical properties of the samples showed a gradual decrease during degradation. We proposed that the degradation of PGA and P(GA-co-LA) fibers proceeded in four stages. A continuous increase in crystallinity during the early stage of degradation and a gradual decline during the later period indicated that preferential hydrolytic degradation occurred in the amorphous regions, followed by a further degradation in the crystalline regions. The cleavage-induced crystallization occurred during the later stage of degradation, contributing to an appreciable decrease in the long period and lamellar thickness of both PGA and P(GA-co-LA) samples. The introduction of LA units into the PGA skeleton reduced the difference in the degradation rate between the crystalline and amorphous regions, and they were simultaneously degraded in the early stage of degradation, leading to a degradation mechanism different from that of the PGA fiber.

20.
Soft Matter ; 17(41): 9447-9456, 2021 Oct 27.
Article in English | MEDLINE | ID: mdl-34612298

ABSTRACT

MDI/BD-block thermoplastic polyurethanes (TPUs) crystallized at different isothermal temperatures and different cooling rates were investigated using multiple techniques. The MDI/BD blocks crystallized in form II when the isothermal temperature was equal to or higher than 150 °C, and in form I at lower isothermal temperatures. Form II had a higher crystal elastic modulus of 6.75 GPa than form I of 1.31 GPa. Form I exhibited contracted conformation, while form II exhibited an extended conformation when viewed from the length of the c-axis in the crystalline state. Based on an analysis of the second derivative in FTIR spectroscopy and simple modeling, the conformation differences were considered to stem from the urethane group's internal bond rotation concerning the phenyl ring and the opening bond angle of phenyl-CH2-phenyl. The generation of form II above 150 °C may be due to the activation of urethane and the flexible methylene elevated by the high temperature. Overall, it was seen that the crystallization of MDI/BD blocks involved a physicochemical change.

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