-
Biochimica Et Biophysica Acta.... Apr 2024Scarring, a prevalent issue in clinical settings, is characterized by the excessive generation of extracellular matrix within the skin tissue. Among the numerous...
Scarring, a prevalent issue in clinical settings, is characterized by the excessive generation of extracellular matrix within the skin tissue. Among the numerous regulatory factors implicated in fibrosis across various organs, the apelin/APJ axis has emerged as a potential regulator of fibrosis. Given the shared attribute of heightened extracellular matrix production between organ fibrosis and scarring, we hypothesize that the apelin/APJ axis also plays a regulatory role in scar development. In this study, we examined the expression of apelin and APJ in scar tissue, normal skin, and fibroblasts derived from these tissues. We investigated the impact of the hypoxic microenvironment in scars on apelin/APJ expression to identify the transcription factors influencing apelin/APJ expression. Through overexpressing or knocking down apelin/APJ expression, we observed their effects on fibroblast secretion of extracellular matrix proteins. We further validated these effects in animal experiments while exploring the underlying mechanisms. Our findings demonstrated that the apelin/APJ axis is expressed in fibroblasts from keloid, hypertrophic scar, and normal skin. The regulation of apelin/APJ expression by the hypoxic environment in scars plays a significant role in hypertrophic scar and keloid development. This regulation promotes extracellular matrix secretion through upregulation of TGF-β1 expression via the PI3K/Akt/CREB1 pathway.
Topics: Animals; Apelin; Apelin Receptors; Cicatrix, Hypertrophic; Fibrosis; Keloid; Phosphatidylinositol 3-Kinases; Humans
PubMed: 38508477
DOI: 10.1016/j.bbadis.2024.167125 -
BioImpacts : BI 2024Remote ischemic conditioning upregulates endogenous protective pathways in response to ischemia-reperfusion injury. This study tested the hypothesis that limb remote...
Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway.
INTRODUCTION
Remote ischemic conditioning upregulates endogenous protective pathways in response to ischemia-reperfusion injury. This study tested the hypothesis that limb remote ischemic per- conditioning (RIPerC) exerts cardioprotective effects via the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS)/apelin pathway.
METHODS
Renal ischemia-reperfusion injury (I/R) was induced by bilateral occlusion of the renal pedicles for 60 minutes, followed by 24 hours of reperfusion; sham-operated rats served as controls. RIPerC was induced by four cycles (5 minutes) of limb ischemia-reperfusion along with bilateral renal ischemia. The functional disturbance was evaluated by renal (BUN and creatinine) and cardiac (troponin I and lactate dehydrogenase) injury biomarkers.
RESULTS
Renal I/R injury increased renal and cardiac injury biomarkers that were reduced in the RIPerC group. Histopathological findings of the kidney and heart were also suggestive of amelioration injury-induced changes in the RIPerC group. Assessment of cardiac electrophysiology revealed that RIPerC ameliorated the decline in P wave duration without significantly affecting other cardiac electrophysiological changes. Further, renal I/R injury increased the plasma (322.40±34.01 IU/L), renal (8.27±1.10 mIU/mg of Protein), and cardiac (68.28±10.28 mIU/mg of protein) angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite (25.47±2.01 & 16.62±3.05 μmol/L) and nitrate (15.47±1.33 & 5.01±0.96 μmol/L) levels; these changes were reversed by RIPerC. Further, renal ischemia-reperfusion injury significantly (=0.047) decreased the renal (but not cardiac) apelin mRNA expression, while renal and cardiac ACE2 (<0.05) and iNOS (=0.043) mRNA expressions were significantly increased compared to the sham group; these effects were largely reversed by RIPerC.
CONCLUSION
Our results indicated that RIPerC protects the heart against renal ischemia- reperfusion injury, likely via interaction of the apelin with the RAS/iNOS pathway.
PubMed: 38505676
DOI: 10.34172/bi.2023.27567 -
Animals : An Open Access Journal From... Mar 2024This study investigated the effects of fish oil (FO), soybean oil (SO), rapeseed oil (RO), peanut oil (PO) and lard oil (LO) on growth, immunity and muscle quality in...
This study investigated the effects of fish oil (FO), soybean oil (SO), rapeseed oil (RO), peanut oil (PO) and lard oil (LO) on growth, immunity and muscle quality in juvenile largemouth bass. After 8 weeks, the results showed that FO and RO could increase weight gain and serum alkaline phosphatase and apelin values compared with LO ( < 0.05). Except lower crude lipid contents, higher amounts of n-3 polyunsaturated fatty acids (15.83% and 14.64%) were present in the dorsal muscle of the FO and RO groups. Meanwhile, FO and RO could heighten mRNA levels of immune defense molecules (lysozyme, hepcidin, and transforming growth factor β1) compared with PO ( < 0.05). While SO could increase potential inflammatory risk via rising counts of white blood cells, platelets, neutrophils and monocytes, and mRNA levels of interleukins (IL-1β, IL-8, IL-12 and IL-15), FO and RO could improve hardness, chewiness and springiness through increasing amounts of hydroxyproline, collagen and lysyl oxidase, and mRNA levels of collagen 1α2 and prolyl hydroxylase in the fish dorsal muscle. Moreover, FO and RO could improve firmness through increasing glycogen and glycogen synthase 1 levels when compared with LO ( < 0.05). Therefore, these results could provide dietary lipid source references during the feeding process of adult largemouth bass.
PubMed: 38473166
DOI: 10.3390/ani14050781 -
European Review For Medical and... Feb 2024Adipose tissue is the largest endocrine organ in the human body, and as its mass changes, the serum levels of the molecules it secretes also change. Visceral adipose... (Observational Study)
Observational Study
Effects of weight intervention-induced changes in pathological fat mass of patients with extreme obesity and anorexia nervosa on adipokines and visceral adipocyte functions: a prospective, comparative, observational study.
OBJECTIVE
Adipose tissue is the largest endocrine organ in the human body, and as its mass changes, the serum levels of the molecules it secretes also change. Visceral adipose tissue index (VAI) is a simple surrogate marker of visceral adipose tissue dysfunction. This study evaluated the effects of changes in fat mass on adipocytokine behavior and VAI in patients with anorexia nervosa (AN) and extreme obesity (EO).
PATIENTS AND METHODS
The study group consisted of three subgroups: Group 1, patients with EO who were candidates for obesity surgery with BMI≥50 kg/m2 (n=20). Group 2, newly diagnosed patients with AN (n=12). Group 3 controls with BMI 20-25 kg/m2 (n=20). The AN and EO groups were followed until at least a 10% weight change before and after the intervention.
RESULTS
Prior to the intervention, EO patients exhibited the lowest levels of apelin, omentin, and adiponectin, while AN patients demonstrated the highest levels of these markers. Leptin and IL-6 were elevated in EO and reduced in AN patients. After treatment, all adipokines and VAI increased in AN patients, and omentin, adiponectin, and IL-6 increased in EO patients, while apelin, leptin, and VAI decreased. The change in each adipocytokine (∆) was positively correlated with the other adipocytokines (p<0.050) and negatively correlated with metabolic and VAI changes (p<0.050). The regression analysis determined that the following variables were associated with the change in adipose tissue mass: Δapelin (OR: 1.061; p=0.028) and Δadiponectin (OR: 1.057; p=0.036).
CONCLUSIONS
In individuals with pathological adipocyte mass, the change in adipocytokine levels in response to weight change is not as expected. The fact that these changes are not seen in the early period of the weight intervention treatment indicates that these patients have compensatory physiological mechanisms to protect them. In addition, using VAI instead of BMI, whose reliability is increasingly questioned because it does not reflect body fat mass, can be considered an alternative. However, there may be modeling errors in the early stages of weight change and in AN and EO patients where metabolic parameters reach extreme values. Therefore, it should be tested in studies where larger patient groups are followed for a more extended period.
Topics: Humans; Leptin; Adipokines; Apelin; Adiponectin; Anorexia Nervosa; Interleukin-6; Prospective Studies; Reproducibility of Results; Obesity, Morbid; Adipocytes
PubMed: 38436178
DOI: 10.26355/eurrev_202402_35474 -
Scientific Reports Mar 2024Abdominal aortic aneurysm (AAA) is a condition characterized by a pathological and progressive dilatation of the infrarenal abdominal aorta. The exploration of AAA...
Abdominal aortic aneurysm (AAA) is a condition characterized by a pathological and progressive dilatation of the infrarenal abdominal aorta. The exploration of AAA feature genes is crucial for enhancing the prognosis of AAA patients. Microarray datasets of AAA were downloaded from the Gene Expression Omnibus database. A total of 43 upregulated differentially expressed genes (DEGs) and 32 downregulated DEGs were obtained. Function, pathway, disease, and gene set enrichment analyses were performed, in which enrichments were related to inflammation and immune response. AHR, APLNR, ITGA10 and NR2F6 were defined as feature genes via machine learning algorithms and a validation cohort, which indicated high diagnostic abilities by the receiver operating characteristic curves. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was used to quantify the proportions of immune infiltration in samples of AAA and normal tissues. We have predicted AHR, APLNR, ITGA10 and NR2F6 as feature genes of AAA. CD8 + T cells and M2 macrophages correlated with these genes may be involved in the development of AAA, which have the potential to be developed as risk predictors and immune interventions.
Topics: Humans; Apelin Receptors; Aortic Aneurysm, Abdominal; Aorta, Abdominal; Algorithms; Machine Learning; Repressor Proteins
PubMed: 38431726
DOI: 10.1038/s41598-024-55941-6 -
Biochimica Et Biophysica Acta.... Apr 2024The abnormal proliferation, migration, and inflammation of vascular smooth muscle cells (VSMCs) play crucial roles in the development of neointimal hyperplasia and...
The abnormal proliferation, migration, and inflammation of vascular smooth muscle cells (VSMCs) play crucial roles in the development of neointimal hyperplasia and restenosis. Exposure to inflammatory cytokines such as platelet-derived growth factor (PDGF)-BB and tumour necrosis factor-alpha (TNF-α) induces the transformation of contractile VSMCs into abnormal synthetic VSMCs. Isoxanthohumol (IXN) has significant anti-inflammatory, antiproliferative, and antimigratory effects. This study aimed to explore the therapeutic impact and regulatory mechanism of IXN in treating neointimal hyperplasia. The present findings indicate that IXN effectively hinders the abnormal proliferation, migration, and inflammation of VSMCs triggered by PDGF or TNF-α. This inhibition is primarily achieved through the modulation of the apelin/AKT or AKT pathway, respectively. In an in vivo model, IXN effectively reduced neointimal hyperplasia in denuded femoral arteries. These results suggest that IXN holds promise as a potential and innovative therapeutic candidate for the treatment of restenosis.
Topics: Humans; Hyperplasia; Cell Proliferation; Proto-Oncogene Proteins c-akt; Tumor Necrosis Factor-alpha; Apelin; Cell Movement; Becaplermin; Neointima; Inflammation; Xanthones
PubMed: 38428686
DOI: 10.1016/j.bbadis.2024.167099 -
Experimental and Therapeutic Medicine Mar 2024Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes, one key feature of which includes renal fibrosis. As apelin is an adipokine closely...
Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes, one key feature of which includes renal fibrosis. As apelin is an adipokine closely related to diabetes, the present study aimed to evaluate apelin-13 expression levels and the relationship between apelin-13 and disease indicators in patients with diabetic kidney disease (DKD). The present case-control study enrolled 70 patients with diabetes, including 31 with diabetic kidney disease (DKD group), 39 without DKD (non-DKD group) and 30 healthy controls. The levels of serum apelin-13 and TGF-β1, the key driver of renal fibrosis, were determined by ELISA. Additionally, age, mean disease duration, weight, blood pressure, fasting blood glucose, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein, cholesterol, urea nitrogen, blood creatinine and 24-hour urinary total protein (24-h UTP) were recorded. The results demonstrated that apelin-13 and TGF-β1 expression levels, age, blood pressure, fasting blood glucose, cholesterol and blood urea nitrogen levels were significantly higher in patients with diabetes compared with the healthy controls (P<0.05). Moreover, apelin-13 and TGF-β1 expression levels, mean disease duration, systolic pressure, blood creatinine, blood urea nitrogen and 24-h UTP were significantly higher in the DKD group compared with the non-DKD group (P<0.05). The estimated glomerular filtration rate (eGFR) was significantly reduced in the DKD group compared with the non-DKD group (P<0.05). Correlation analysis demonstrated a negative correlation between apelin-13 and eGFR expression and a positive correlation between apelin-13 expression and 24-h UTP in both the DKD and non-DKD groups (P<0.05). A negative correlation was also demonstrated between apelin-13 and TGF-β1 expression levels in the DKD group and non-DKD groups (both P<0.05). In conclusion, apelin-13 and TGF-β1 expression levels were significantly higher in the DKD group compared with those in the non-DKD group. Additionally, apelin-13 expression was negatively correlated with TGF-β1 expression in the DKD and non-DKD groups. Therefore, apelin-13 could potentially be used in the future as an indicator of renal fibrosis or destruction in patients with DKD. The present trial was retrospectively registered in the Chinese Clinical Trial Registry (trial registration no. ChiCTR2200060945) on 14.06.2022.
PubMed: 38361517
DOI: 10.3892/etm.2024.12398 -
PloS One 2024Delayed diagnosis and inadequate treatment of infectious and inflammatory diseases, such as Brucella, lead to high rates of mortality and morbidity. The aim of our study...
BACKGROUND
Delayed diagnosis and inadequate treatment of infectious and inflammatory diseases, such as Brucella, lead to high rates of mortality and morbidity. The aim of our study was to investigate the association between serum levels of apelin, presepsin, and irisin with inflammation, laboratory parameters, and blood culture in patients with brucella.
PATIENTS AND METHODS
This prospective case-control study involves 30 patients with brucellosis and 30 healthy, matched control subjects. Thirty patients who were diagnosed with brucellosis were aged ≥ 18 years. Blood samples were taken from the patients on the first day they were diagnosed with brucellosis. The values of irisin, presepsin, and apelin were studied. In addition, blood samples were also taken from 30 healthy individuals for the control group. Irisin, presepsin, and apelin values that were measured in the patients on the first day were compared with those values measured in the control group.
RESULTS
The sex and age statuses of the subjects are matched among the groups. The levels of irisin were significantly higher in patients with brucellosis compared to the control group (p<0.045). There was no significant difference between the two groups in terms of apelin and presepsin levels (p values 0.087 and 0.162, respectively). There was a positive correlation between irisin levels and elevated ALT levels, as well as positive blood cultures.
CONCLUSIONS
It appears that the measurement of irisin levels may be beneficial in patients with brucellosis. Irisin can be used as a diagnostic marker for brucella infection and may greatly clinicians to predict the severity disease and treatment response.
Topics: Humans; Brucella; Apelin; Case-Control Studies; Fibronectins; Brucellosis; Biomarkers; Peptide Fragments; Lipopolysaccharide Receptors
PubMed: 38359069
DOI: 10.1371/journal.pone.0297550 -
Heliyon Feb 2024Sepsis-induced myocardial dysfunction (SMD) is the major cause of death in sepsis. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing...
Sepsis-induced myocardial dysfunction (SMD) is the major cause of death in sepsis. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis contributes to the occurrence and development of SMD. Although Apelin confers direct protection against SMD, the potential mechanisms remain unclear. This study aimed to determine whether Apelin protects against SMD via regulation of NLRP3-mediated pyroptosis of cardiomyocytes. Experimental SMD was induced in wild-type (WT) control mice and Apelin knockout (Apelin) mice by cecal ligation and puncture (CLP). Neonatal mouse cardiomyocytes (NMCs) were treated with lipopolysaccharide (LPS) to simulate the physiological environment of SMD . The expression of Apelin was greatly decreased in the plasma from septic patients and septic mouse heart. Knockout of Apelin aggravated SMD, evidenced by decreased cardiac function, and increased cardiac fibrosis and NLRP3 inflammasome and pyroptosis levels in CLP-treated Apelin mice compared with WT mice. Overexpression of Apelin activated the AMPK pathway and thereby inhibited NLRP3 inflammasome-mediated pyroptosis of NMCs induced by LPS These protective effects were partially abrogated by AMPK inhibitor. In conclusion, Apelin attenuated SMD by inhibiting NLRP3-mediated pyroptosis via activation of the AMPK pathway. Apelin may serve as a promising therapeutic target for SMD.
PubMed: 38356599
DOI: 10.1016/j.heliyon.2024.e24568 -
Scientific Reports Feb 2024In contrast to adult mammals, zebrafish display a high capacity to heal injuries and repair damage to various organs. One of the earliest responses to injury in adult...
In contrast to adult mammals, zebrafish display a high capacity to heal injuries and repair damage to various organs. One of the earliest responses to injury in adult zebrafish is revascularization, followed by tissue morphogenesis. Tissue vascularization entails the formation of a blood vessel plexus that remodels into arteries and veins. The mechanisms that coordinate these processes during vessel regeneration are poorly understood. Hence, investigating and identifying the factors that promote revascularization and vessel remodeling have great therapeutic potential. Here, we revealed that fin vessel remodeling critically depends on Apela peptide. We found that Apela selectively accumulated in newly formed zebrafish fin tissue and vessels. The temporal expression of Apela, Apln, and their receptor Aplnr is different during the regenerative process. While morpholino-mediated knockdown of Apela (Mo-Apela) prevented vessel remodeling, exogenous Apela peptide mediated plexus repression and the development of arteries in regenerated fins. In contrast, Apela enhanced subintestinal venous plexus formation (SIVP). The use of sunitinib completely inhibited vascular plexus formation in zebrafish, which was not prevented by exogenous application. Furthermore, Apela regulates the expression of vessel remolding-related genes including VWF, IGFPB3, ESM1, VEGFR2, Apln, and Aplnr, thereby linking Apela to the vascular plexus factor network as generated by the STRING online database. Together, our findings reveal a new role for Apela in vessel regeneration and remodeling in fin zebrafish and provide a framework for further understanding the cellular and molecular mechanisms involved in vessel regeneration.
Topics: Animals; Animal Fins; Apelin Receptors; Mammals; Peptide Hormones; Regeneration; Vascular Remodeling; Zebrafish; Zebrafish Proteins
PubMed: 38355946
DOI: 10.1038/s41598-023-50677-1