Home Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease
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Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease

  • Qiang Wang , Bo Zheng , Peng Chen and Yan Lei EMAIL logo
Published/Copyright: January 18, 2022
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Open Medicine
From the journal Open Medicine Volume 17 Issue 1

Abstract

Leptin and proprotein convertase subtilisin kexin 9 (PCSK9) play an important role in regulating blood lipid concentration. Recently, they have been found to show the ability to independently regulate the immune response. Vascular immune response has an important pathological function in the development of coronary heart disease (CHD) and thrombosis. The aim of this study was to explore the relationship between leptin, PCSK9, and vascular endothelial cell related inflammatory factors. First, detailed clinical information were collected and analyzed for 27 patients with stable CHD and corresponding 27 healthy controls. Second, using liquid-phase protein chip technology, leptin, PCSK9, and vascular-related inflammatory factors, such as E-selectin, vascular cell adhesion protein 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-γ), and interleukin-17 (IL-17), were detected on the same platform. Finally, the correlation between leptin, PCSK9, and the inflammatory factors was analyzed. Through collecting clinical information of patients, it was suggested that there was a significant positive correlation between leptin and blood lipid level in CHD. Compared with healthy people, the levels of leptin, PCSK9, E-selectin, and ICAM-1 were significantly high in patients with CHD. There was a high positive correlation between leptin and E-selectin, ICAM-1, IFN-γ, and IL-17. Also, a high positive correlation between PCSK9 and E-selectin, IFN-γ, and IL-17 concentrations was observed. In general, leptin and PCSK9 may not only be able to regulate lipid metabolism, but may also be able to regulate inflammation in CHD.

Keywords: coronary heart disease; vascular inflammation; leptin; PCSK9

1 Introduction

Leptin is a protein secreted by adipose tissue, which is widely believed to participate in the regulation of glycometabolism, fatty acid, and energy metabolism. It can reduce food intake, increase energy release, inhibit the synthesis of adipocytes, and then reduce weight. The recent studies found that leptin can also regulate immune inflammatory response [1,2,3,4]. In the innate immunity, leptin promotes natural killer cell activation, neutrophil chemotaxis, and macrophage secretion of tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-12 (IL-12). In the adaptive immunity, leptin stimulates the proliferation of immature T cells and inhibits CD4+CD25+Foxp3+ regulatory T cells. Importantly, researchers found that leptin increased the differentiation of Th17 cells in Systemic Lupus Erythematosus patients [5,6]. However, it is still unclear whether leptin is associated with vasculitis endothelial cell inflammation in patients with coronary heart disease (CHD).

Proprotein convertase subtilisin kexin 9 (PCSK9), as a neuronal apoptotic regulatory invertase, not only participates in liver regeneration and regulates neuronal apoptosis, but also affects low-density lipoprotein (LDL) internalization by reducing the number of LDL-receptor (LDLR) on hepatocytes, so that the LDL in blood cannot be cleared, leading to hypercholesterolemia [7]. PCSK9 is a central participant in atherosclerosis and a key immune effect of oxidized LDL inducing dendritic cell maturation and plaque T cell activation [8]. This may directly affect atherosclerosis and cardiovascular disease.

Vascular endothelial cell inflammation is the key node of thrombosis, and adhesion molecules play a decisive role in the early stage of thrombosis [9]. There are few reports on the correlation of leptin, PCSK9, and CHD vascular inflammation in CHD patients. So, the aim of this study is to explore the relationship between serum leptin, PCSK9, endothelial cell adhesion factors, and Interleukin-17 (IL-17) levels in CHD patients. This study will help to clarify whether PCSK9 and leptin are involved in vascular inflammation, and not just play a pathological role in CHD by regulating blood lipids.

2 Material and methods

2.1 Samples and baseline

The study was ethically reviewed by the Medical Experimental Center of the Chinese Academy of Traditional Chinese Medicine, and informed consent was issued by each patient. Samples and Healthy controls were obtained from Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine and Affiliated Hospital of Binzhou Medical University. Serum samples and clinical information of 27 patients with CHD and 27 healthy controls were collected in this study. Diagnosis of CHD was accomplished by coronary Computed Tomography or coronary angiography. There was no significant difference in age and sex between the two groups.

2.2 Liquid-phase protein chip

Liquid-phase protein chip technology was used to detect the level of protein markers in this study. The specific methods were described as follows. Commercial test kits were purchased from RD Biotechnology Company, which can be used to detect seven factors including Leptin, PCSK9, Interferon-gamma (IFN-γ), IL-17, E-selectin, vascular cell adhesion protein 1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1). First, the serum was mixed with the magnetic beads coated with antibodies. The diluted volume of the serum was 1:2, and the reaction was carried out at room temperature for 1 h and then washed 3 times with a magnet washer for 5 min each time. The second antibody corresponding to the 7 proteins was added and reacted at room temperature for 1.5 h. Fluorescent pigments were added and reacted at room temperature for 10 min. After cleaning, the fluorescence value was read by an instrument, and the concentration of the sample was calculated according to the standard curve.

2.3 Statistics

Differences in clinical information and protein concentration among different ethnic groups were examined by t-test. All the drawings in this article were executed by Microsoft Excel. The fitting of the standard curve for protein concentration determination was based on 4PL method. P value less than 0.05 was considered to have significant statistical difference.

3 Results

3.1 Clinical parameters and concentration of leptin and PCSK9

First, 27 stable CHD patients (62.52 ± 10.38 years old; 15 males and 12 females) and 27 healthy controls (60.0 ± 11.24 years; 15 males and 12 females) were recruited (Table 1). There was no statistical difference (P < 0.05) in age and gender data between the two groups. The male patients with CHD were more than the female patients. Male patients with stable CHD were younger than female patients (P < 0.05). The LDL-C, CHO, apolipoprotein B (Apob), and apolipoprotein A1 (Apoa1) levels of female patients with stable CHD were higher than that of male patients, and they were statistically significant (P < 0.05). There was no significant difference in other indexes between the two groups (P > 0.05). It showed that female had higher risk of CHD than male. According to the standard curve of 65 years old, CHD patients were divided into two groups. There was no difference in the factors between the two groups (P > 0.05).

Table 1

Clinical information of patients with CHD

No. Gender Age LDL-C CK-MB CHO Apob Apoa1 HDL-C TG CRP Sd-LDL THCY
1 M 68 2.39 12.5 4.19 0.92 1.25 1.36 1.85 71.41 205 18.42
2 F 79 1.37 10.9 2.62 0.51 1.16 1.1 0.89 1.45 145 14.93
3 F 64 3.59 10.8 5.26 1.26 1.44 1.39 1.93 19.5 360 9.95
4 M 66 1.77 16.8 3.12 0.76 1.12 1.06 1.39 1.38 211 17.82
5 M 55 3.94 12.8 5.15 1.37 1.14 1.02 1.72 0.27 509 13.55
6 F 66 1.48 14 3.02 0.71 1.2 0.84 2.55 0.63 287 10.64
7 M 57 2.04 23.9 3.04 0.74 0.87 1.04 0.47 7.06 126 27.26
8 F 76 1.62 8.7 3.17 0.66 1.18 1.12 1.66 0.82 149 17.26
9 F 75 3.04 16.8 5.28 1.19 1.63 1.86 1.74 21.46 301 19.3
10 M 72 2.01 16.5 3.07 0.79 1.12 1.02 1.04 0.26 256 14.37
11 M 34 2.01 12 3.35 0.79 1.27 1.04 1.95 0.92 285 12.6
12 M 58 1.37 15.2 2.43 0.61 0.92 0.92 0.73 1.3 165 12.26
13 M 45 1.63 19.2 3.05 0.58 1.45 1.38 0.79 1.23 141 10.86
14 M 55 1.73 12.8 3.16 0.63 1.33 1.41 1.12 0.23 184 12.66
15 F 65 4 10.8 5.22 1.32 1.22 1.17 1 2.51 228 10.83
16 F 59 2.61 12.2 3.62 0.96 0.83 0.67 2.1 2.22 425 7.31
17 M 65 2.03 1.1 3.55 0.85 0.96 1.08 1.59 2.18 260 1.25
18 F 63 3.36 25.1 4.5 1.05 1.34 1.23 1.14 1.35 304 22.81
19 M 64 2.31 20.8 3.59 0.86 1.21 1.27 0.88 20.25 218 12.29
20 F 55 1.9 13.2 3.51 0.79 1.49 1.26 2.15 2.38 300 9.53
21 M 58 1.26 9.9 2.5 0.51 1.1 0.94 2.07 0.41 189 14.11
22 F 65 2.78 13.2 5.1 1.21 1.6 1.24 4.24 2 623 12.53
23 M 44 1.97 10.9 2.93 0.74 0.84 0.85 1.09 0.61 186 16.88
24 F 76 2.11 24.4 3.56 0.76 1.5 1.55 1.08 0.28 199 14.4
25 F 64 3.93 15.9 5.23 1.33 1.25 1.25 1.08 0.48 317 12.26
26 M 73 1.45 7.3 2.58 0.62 1.02 0.84 2.06 0.81 209 10.54
27 M 67 1.7 28.2 2.8 0.64 0.64 1.04 1.03 0.23 187 12.29
Unit — — mM U/L mM g/L g/L mM mM mM mg/L µM
Mean 62.52 2.27 14.66 3.65 0.86 1.19 1.15 1.53 6.06 258.11 13.66

LDL-C: Low-density lipoprotein cholesterol; CK-MB: Creatine kinase myocardial Isoenzymes; CHO: Total cholesterol; Apo: Apolipoprotein; Glu: Glucose; HDL-C: High-density lipoprotein cholesterol; TG: Total triglycerides; CRP: C-reactive protein; Sd-LDL: Small and dense low density lipoprotein; THCY: Homocysteine.

3.2 Association studies of endothelial cell adhesion factors with leptin and PCSK9 in CHD patients

Endothelial cell adhesion inflammation factors in patients with CHD was significantly higher than healthy controls (P < 0.05). The results are shown in Figure 1. PCSK9 and leptin were also highly expressed in CHD patients, and they may be related to lipid regulation and metabolism, there was also a significant relationship between leptin and blood lipid level. The levels of leptin were positively correlated with blood total triglycerides (TG) levels (Figure 2). There was a significant relationship between PCSK9 and E-selectin, IFN-γ, and IL-17. Also, there was a significant relationship between leptin and endothelial cell inflammatory factors (ICAM-1, E-selectin, and IFN-γ) and IL-17 (Figure 3). However, the specific mechanism between them and the inflammatory factors, especially endothelial cells inflammation, is still unclear.

Figure 1 Endothelial cell adhesion factors in patients with CHD was significantly higher than that in healthy controls: PCSK9 level in CHD and HC subjects; leptin; E-selectin; and VCAM-1. CHD: coronary heart disease; HC: Healthy controls.
Figure 1

Endothelial cell adhesion factors in patients with CHD was significantly higher than that in healthy controls: PCSK9 level in CHD and HC subjects; leptin; E-selectin; and VCAM-1. CHD: coronary heart disease; HC: Healthy controls.

Figure 2 The levels of leptin were positively correlated with blood TG levels. TG: total triglycerides.
Figure 2

The levels of leptin were positively correlated with blood TG levels. TG: total triglycerides.

Figure 3 Significant relationship between leptin, PCSK9, and endothelial cell adhesion factors was observed. Correlation lines between leptin and IL-17 (a), IFN-γ (b), ICAM-1 (c), E-selectin (d); and Correlation lines between IL-17, E-selectin, IFN-γ, and PCSK9 (e).
Figure 3

Significant relationship between leptin, PCSK9, and endothelial cell adhesion factors was observed. Correlation lines between leptin and IL-17 (a), IFN-γ (b), ICAM-1 (c), E-selectin (d); and Correlation lines between IL-17, E-selectin, IFN-γ, and PCSK9 (e).

4 Discussion

Leptin is a fat cytokine secreted mainly by white adipose tissue and involved in a variety of pathophysiological processes, including maintaining energy balance, regulating immune and inflammatory responses, and bone metabolism [10]. Leptin is an important intermediary for the interaction between nutritional status and neuroendocrine-immune function in vivo [11], and the content of Leptin is closely related to the occurrence and development of various autoimmune diseases. Leptin is an inflammatory cytokine which was involved in the pathogenesis of rheumatoid arthritis and may be an indicator of disease activity and joint failure, as well as a potential therapeutic target [12,13]. Therefore, the role of leptin as a new type of immunomodulatory agent in inflammatory response has attracted more and more attention. In this study, It was suggested that leptin also participates in the inflammatory process of vascular CHD.

PCSK9, as a neuronal apoptotic regulatory invertase, participates in liver regeneration and regulates neuronal apoptosis, and affects LDL internalization by reducing the number of LDLR on hepatocytes. As a serine protease, PCSK9 not only can degrade LDLR and elevate LDL cholesterol level in blood, but also has many other biological functions, such as participating in nervous system development, neuronal apoptosis, regulating sodium channel, islet cell function, etc. [7]. PCSK9 is produced by synthesizing PCSK9 zymogen in endoplasmic reticulum, which reacts with self-catalysis in endoplasmic reticulum or golgi body, releasing properties to form mature protease, and secreting into blood immediately. Elevated LDL cholesterol is a major risk factor for atherosclerotic cardiovascular disease. PCSK9, a new generation drug target of lipid-lowering frontier drug, provides a new therapeutic model to combat LDL cholesterol [14]. It is a great progress for lowering lipid after statins, especially in patients with statin intolerance, resistance, and familial hereditary hypercholesterolemia. In fact, PCSK9 inhibitors not only reduce LDL cholesterol but also reduce cardiovascular risk in terms of anti-inflammation according to a Phase III clinical study conducted by Amgen in March 2018 [15]. There was a significant relationship between PCSK9 and E-selectin, IFN-γ, and IL-17. This suggests that leptin and PCSK9 may independently participate in the development of CHD through inflammation regulation. They have potential value as independent indexes for evaluating inflammation and risk assessment of stable CHD.

Inflammation and inflammatory factors have been continuously concerned in the pathogenesis of cardiovascular disease; the plasma levels IL-9 was detected to be associated with cardiopulmonary dysfunction and all-cause mortality in chronic heart failure [16,17]. CHD is a pathological process characterized by chronic inflammation. The occurrence and development of CHD is always accompanied by inflammation [18,19]. Inflammatory mediators such as ICAM-1, VCAM-1, and E-selectin have been proved to play an important role in the upstream of CHD process, significantly increasing the risk of plaque progression, instability, and cardiovascular events [20]. This study explored the relationship between leptin, PCSK9, endothelial cell-related inflammatory adhesion factors, and IL-17. The results suggested that there was a correlation between them. This provided direct evidence for their association with vascular endothelial cells and autoimmunity, and provided a possible theory for guiding the use of their inhibitors. As an autoimmune-related inflammatory factor, IL-17 levels in serum of patients with CHD were not significantly different from those of healthy people, suggesting that the autoimmune properties of CHD were not significant. However, there are still some limitations in this study, such as the small number of samples and the lack of multi-center dynamic research, which is the next research we need to do.

These authors were contributed equally.

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Acknowledgements

Not applicable.

  1. Funding information: This study was supported by grants from the Fundamental Research Funds for the Central public welfare research institutes of China (ZZ11-113 and ZZ13-YQ-034); and the National Natural Science Foundation of China (81703865 and 81673822).

  2. Author contributions: Q.W. and B.Z.: designed and collected the samples and writing original draft; P.C.: carried out the experiments, writing, reviewing, and editing; and Y.L.: designed the concept of study and revised the manuscript.

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Data availability statement: The data in this study are available from the corresponding author on reasonable request.

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Received: 2020-10-08
Revised: 2021-06-27
Accepted: 2021-10-28
Published Online: 2022-01-18

© 2022 Qiang Wang et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
https://doi.org/10.1515/med-2021-0400
Keywords for this article
coronary heart disease; vascular inflammation; leptin; PCSK9
Creative Commons
BY 4.0

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  3. A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma
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  7. Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data
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  22. lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells
  23. circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer
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  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
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  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
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  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
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  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
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