The Role of Secreted Frizzled-Related Protein 5 (Sfrp5) in Overweight and Obesity in Childhood and Adolescence.

Background/Objective: Secreted frizzled-related protein 5 (Sfrp5) is an anti-inflammatory adipokine that has been implicated in the pathophysiology of obesity and its metabolic complications. Despite the fact that numerous studies have been carried out in adults, limited data on Sfrp5 exist for youth, especially in relation to overweight and obesity. Methods: In our study, we assessed the concentrations of Sfrp5, total oxidative (TOS) and antioxidative (TAS) status, high-sensitivity C-reactive protein (hs-CRP), and several cytokines (IL-1α, IL-1ß, IL-2, IL-6, IL-8, IL-12, TNF-α) in 120 children and adolescents (mean age ± SE: 11.48 ± 0.25 years; 48 prepubertal, 72 pubertal; 74 males and 46 females) before and 1 year after the implementation of a personalized, structured, lifestyle intervention program of healthy diet, sleep, and physical exercise. Results: Based on the body mass index (BMI), participants were categorized as having morbid obesity (n = 63, 52.5%), obesity (n = 21, 17.5%), overweight (n = 22, 18.33%), or normal BMIs (n = 14, 11.67%), based on the International Obesity Task Force (IOTF) cut-off points. Following the 1-year lifestyle intervention program, a significant improvement in anthropometric measurements (BMI, BMI-z score, diastolic blood pressure, WHR, and WHtR), body-composition parameters, hepatic enzymes, lipid profile, inflammation markers, and the insulin-sensitivity profile (HbA1C, HOMA index) was observed in all subjects. Sfrp5 decreased in subjects with obesity (p < 0.01); however, it increased significantly (p < 0.05) in patients with morbid obesity. Linear regression analysis indicates that TNF-α and systolic blood pressure were the best positive predictors and hs-CRP was the best negative predictor for Sfpr5 concentration at initial assessment and glucose concentration for ΔSfrp5, while TNF-α and TAS were the best positive predictors for Sfpr5 concentration at annual assessment. Conclusions: These results indicate that Sfrp5 is associated with severe obesity and is increased following weight loss in children and adolescents with morbid obesity. It is also related to metabolic homeostasis, as well as inflammation and oxidative status.

Expression Pattern of PDE4B, PDE4D, and SFRP5 Markers in Colorectal Cancer.

Background and Objectives: Colorectal cancer (CRC) is the most frequently diagnosed malignant disease of the gastrointestinal system, and new diagnostic and prognostic markers are needed to elucidate the complete tumor profile. Materials and Methods: We used CRC tumor tissues (Dukes' A-D) and adjacent noncancerous tissues of 43 patients. Immunohistochemistry was used to examine the expression of phosphodiesterase 4B (PDE4B), phosphodiesterase 4D (PDE4D), and secreted frizzled related protein 5 (SFRP5) markers. We also analyzed the expression levels of PDE4B, PDE4D, and SFRP5 in CRC tissues compared to control tissues using RNA-sequencing data from the UCSC Xena browser. Results: In CRC stages, the distribution of PDE4B-positive cells varied, with differing percentages between epithelium and lamina propria. Statistically significant differences were found in the number of PDE4B-positive epithelial cells between healthy controls and all CRC stages, as well as between different CRC stages. Similarly, significant differences were observed in the number of PDE4B-positive cells in the lamina propria between healthy controls and all CRC stages, as well as between different CRC stages. CRC stage Dukes' C exhibited a significantly higher number of PDE4B-positive cells in the lamina propria compared to CRC stage Dukes' B. Significant differences were noted in the number of PDE4D-positive epithelial cells between healthy controls and CRC stages Dukes' A, B, and D, as well as between CRC stage Dukes' C and stages A, B, and D. CRC stage Dukes' A had significantly more PDE4D-positive cells in the lamina propria compared to stage D. Significant differences were also observed in the number of SFRP5-positive cells in the lamina propria between healthy controls and all CRC stages, as well as between CRC stages Dukes' A and D. While the expression of PDE4D varied across CRC stages, the expression of SFRP5 remained consistently strong in both epithelium and lamina propria, with significant differences noted mainly in the lamina propria. The expression levels of PDE4B, PDE4D, and SFRP5 reveal significant differences in the expression of these genes between CRC patients and healthy controls, with notable implications for patient prognosis. Namely, our results demonstrate that PDE4B, PDE4D, and SFRP5 are significantly under-expressed in CRC tissues compared to control tissues. The Kaplan-Meier survival analysis and the log-rank (Mantel-Cox) test revealed distinct prognostic implications where patients with lower expression levels of SFRP5 exhibited significantly longer overall survival. The data align with our immunohistochemical results and might suggest a potential tumor-suppressive role for these genes in CRC. Conclusions: Considering significantly lower gene expression, aligned with our immunohistochemical data in tumor tissue in comparison to the control tissue, as well as the significantly poorer survival rate in the case of its higher expression, we can hypothesize that SFRP5 is the most promising biomarker for CRC out of the observed proteins. These findings suggest alterations in PDE4B, PDE4D, and SFRP5 expression during CRC progression, as well as between different stages of CRC, with potential implications for understanding the molecular mechanisms involved in CRC development and progression.

Role of SFRP5 in Non-Small Cell Lung Cancer and Its Correlation with SUV of 18F-FDG PET-CT.

Aim: This study aimed to evaluate the relationship between secreted frizzled-related protein 5 (SFRP5) expression and fluorine 18-fluoro-deoxyglucose (18 F-FDG) uptake imaged with positron emission tomography/tomography (PET/CT) in patients with non-small cell lung cancer (NSCLC). In addition, we sought to elucidate the potential role and mechanism of action of SFRP5 in NSCLC.Materials and methods: The maximum standardized uptake value (SUVmax) of the lesions was calculated. SFRP5 expression was analyzed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The correlation between SFRP5 expression and SUVmax was evaluated using Pearson's correlation analysis. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, wound healing, and transwell assays were used to analyze cell viability, apoptosis, migration, and invasion, respectively.Results and conclusion: The results indicated that the SUVmax was higher in patients with NSCLC than that in healthy volunteers. Moreover, SFRP5 expression was lower in tissues from the four types of NSCLC than that in the adjacent normal tissues. SUVmax negatively correlated with SFRP5 expression in the four types of NSCLC. In addition, up-regulation of SFRP5 decreased the viability, migration, and invasion abilities, and increased apoptosis of NSCLC cells. Furthermore, SFRP5 inhibited the Wnt/ß-catenin pathway in NSCLC cells. In conclusion, SFRP5 modulates the biological behaviors of NSCLC through Wnt/ß-catenin pathway.

Small Peptide Derived from SFRP5 Suppresses Melanogenesis by Inhibiting Wnt Activity.

Melanocytes, located in the epidermis' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and ß-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and ß-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.

Diagnostic and prognostic significance of circulating secreted frizzled-related protein 5 in colorectal cancer.

BACKGROUND: Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) METHODS: Plasma cSFRP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64). RESULTS: Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II-III CRC (univariate: HR 1.82, 95% CI: 1.02-3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12-4.88, p = 0.015). CONCLUSION: This study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II-III disease.

Secreted frizzled-related protein 5 overexpression reverses oxLDL-induced lipid accumulation in human vascular smooth muscle cells.

Atherosclerosis (AS) is the major cause of multiple cardiovascular diseases. In addition, the lipid accumulation of human vascular smooth muscle cells (HVSMCs) can cause the occurrence of AS. Secreted frizzled-related protein 5 (Sfrp5) was known to be downregulated in AS; however, the detailed function of Sfrp5 in HVSMCs remains unclear. Specifically, we found that Sfrp5 expression in oxLDL-treated HVSMCs was downregulated. Sfrp5 overexpression inhibited the viability of HVSMCs induced by oxLDL. In addition, oxLDL-induced proliferation and migration in HVSMCs were abolished by Sfrp5 overexpression. Sfrp5 overexpression reduced oxLDL-caused oxidative stress, lipid accumulation, and inflammation in HVSMCs. Meanwhile, oxLDL treatment increased the expressions of Wnt5a, c-Myc, and ß-catenin in HVSMCs, while this phenomenon was rescued by Sfrp5 overexpression. Furthermore, the inhibitory effect of Sfrp5 upregulation on the viability and migration of HVSMCs was reversed by R-spondin 1. These results indicate that Sfrp5 overexpression could reverse oxLDL-induced lipid accumulation in HVSMCs through inactivating Wnt5a/ß-catenin signaling pathway.

SFRP5 Partially Inhibits the Proliferation and Migration of Airway Smooth Muscle Cells in Children with Asthma by Regulating the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: Childhood asthma is a chronic inflammatory disease of the respiratory tract characterized by bronchial inflammation, airway hyperresponsiveness, airflow disorder, and obstruction. Secreted frizzled-related protein 5 (SFRP5) may be associated with respiratory inflammatory diseases. This study investigated the effect of SFRP5 on human airway smooth muscle cells (HASMCs) to provide new ideas for treating asthma. METHODS: A total of 30 children with asthma and 30 children who had a physical examination at the same time were selected and divided into asthma and healthy groups. Serum SFRP5 levels were determined by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR). Lipofectamine 2000™ regent was used to transfect the SFRP5 overexpression plasmid (pc-SFRP5) or corresponding negative control (pc-NC) into HASMCs. HASMCs were treated with 10 µg/L platelet-derived growth factor-BB (PDGF-BB), which is an inducer to mimic the asthma-like condition at the cellular level of childhood asthma. HASMCs were divided into control, PDGF-BB (PDGF-BB treatment), PDGF-BB+pc-NC (pc-NC transfection and PDGF-BB treatment), and PDGF-BB+pc-SFRP5 (pc-SFRP5 transfection and PDGF-BB treatment) groups. Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assay. Cell migration was detected by Transwell assay. The protein expression was detected by western blot. RESULTS: Serum SFRP5 expression in the asthmatic group was decreased versus the healthy group (p < 0.0001). Induction of PDGF-BB decreased SFRP5 expression in HASMCs (p < 0.01). SFRP5 expression in the pc-SFRP5 group was increased (p < 0.01). The proliferation and migration of HASMCs increased after PDGF-BB treatment (p < 0.001, p < 0.0001), indicating that the asthma model was successfully inducted in vitro. Moreover, the expression of ß-catenin, cellular-myelocytomatosis viral oncogene (c-Myc), and cyclinD1 proteins in HASMCs increased after PDGF-BB treatment (p < 0.0001). SFRP5 overexpression partly inhibited PDGF-BB-induced proliferation, migration, and expressions of ß-catenin, c-Myc, and cyclinD proteins in HASMCs (p < 0.01, p < 0.001, p < 0.0001). CONCLUSIONS: Serum SFRP5 expression decreases in children with asthma. SFRP5 overexpression partially inhibits PDGF-BB-induced HASMC proliferation and migration by regulating the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt)/ß-catenin pathway.

Research Progress on the Mechanism of the SFRP-Mediated Wnt Signalling Pathway Involved in Bone Metabolism in Osteoporosis.

Osteoporosis (OP) is a metabolic bone disease linked to an elevated fracture risk, primarily stemming from disruptions in bone metabolism. Present clinical treatments for OP merely alleviate symptoms. Hence, there exists a pressing need to identify novel targets for the clinical treatment of OP. Research indicates that the Wnt signalling pathway is modulated by serum-secreted frizzled-related protein 5 (SFRP5), potentially serving as a pivotal regulator in bone metabolism disorders. Moreover, studies confirm elevated SFRP5 expression in OP, with SFRP5 overexpression leading to the downregulation of Wnt and ß-catenin proteins in the Wnt signalling pathway, as well as the expression of osteogenesis-related marker molecules such as RUNX2, ALP, and OPN. Conversely, the opposite has been reported when SFRP5 is knocked out, suggesting that SFRP5 may be a key factor involved in the regulation of bone metabolism via the Wnt signalling axis. However, the molecular mechanisms underlying the action of SFRP5-induced OP have yet to be comprehensively elucidated. This review focusses on the molecular structure and function of SFRP5 and the potential molecular mechanisms of the SFRP5-mediated Wnt signalling pathway involved in bone metabolism in OP, providing reasonable evidence for the targeted therapy of SFRP5 for the prevention and treatment of OP.

Efficacy of Yisui granule on myelodysplastic syndromes in SKM-1 mouse xenograft model through suppressing Wnt/ß-catenin signaling pathway.

OBJECTIVE: To unmask the underlying mechanisms of Yisui granule (, YSG) for the treatment of Myelodysplastic syndromes (MDS). METHODS: Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety, assess its effect on overall survival (OS), and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5 (sFRP5) gene and suppressing Wnt/ß-catenin pathway. Bisulfite amplicon sequencing was applied to detect the level of methylation of the sFRP5 gene; western blotting, immunofluorescence staining, and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1 (DNMT1), sFRP5, and other Wnt/ß-catenin pathway-related mRNA and protein expression. RESULTS: The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine, improved OS, and reduced long-term adverse effects in the long term. Mechanically, YSG reduced the expression of DNMT1 methyltransferase, decreased the methylation, and increased the expression of the Wnt/ß-catenin pathway antagonist-sFRP5. Furthermore, components of the Wnt/ß-catenin pathway, including Wnt3a, ß-catenin, c-Myc, and cyclinD1, were down-regulated in response to YSG, suggesting that YSG could treat MDS by demethylating the sFRP5 gene and suppressing the Wnt/ß-catenin pathway. CONCLUSIONS: Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model, providing an alternative solution for treating MDS.

The synergy of serum SFRP5 levels and the TyG index in predicting coronary artery disease and prognosing major adverse cardiovascular events.

BACKGROUND AND AIMS: Secreted frizzled-related protein 5 (SFRP5) is a member of the SFRP family that is known for its potent anti-inflammatory properties. Nevertheless, little is known regarding the relevance of SFRP5 in coronary artery disease (CAD). The current study examined the correlation between serum levels of SFRP5 and the triglyceride-glucose (TyG) index in patients who underwent coronary angiography (CAG) as a component of cardiovascular assessment and for the purpose of prognosis evaluation. METHODS: A total of 310 hospitalized patients were enrolled in this study between May 2021 and March 2022 and were divided into three groups based on their CAG results and SYNTAX (synergy between PCI with TAXUS drug-eluting stent and cardiac surgery) scores: the control group, mild lesion group, and moderate-severe lesion group. Univariate and multivariate analyses were employed to investigate the relationships between changes in patients and clinical variables. To investigate the impact of the TyG index and serum SFRP5 levels on the occurrence of major adverse cardiovascular events (MACEs), Kaplan‒Meier curves were plotted. Serum SFRP5 levels were measured utilizing an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The serum SFRP5 levels significantly decreased with the increasing severity and complexity of CAD, while the TyG index significantly increased (P < 0.001). Moreover, a significant negative correlation was observed between the serum SFRP5 levels and the TyG index (r = -0.312, P < 0.001). SFRP5 exerts a protective role in different groups of patients. The area under the receiver operating characteristic (ROC) curve indicated that an SFRP5 concentration > 115.58 pg/mL was the best predictive value for CAD (OR:0.87, P < 0.001). MACEs were significantly associated with serum SFRP5 levels and the TyG index, as indicated by both univariate and multivariate Cox regression analyses (P < 0.001). Furthermore, Kaplan‒Meier analysis indicated that as the TyG index decreased and SFRP5 levels increased, the occurrence of MACEs decreased (P < 0.001). Patients with a concentration of SFRP5 > 115.58 pg/mL and a TyG index < 8.49 exhibited a better prognosis for avoiding MACEs (P < 0.001). CONCLUSION: These results suggest that the collaboration between serum SFRP5 levels and the TyG index holds promise in predicting CAD and its prognosis.

Concentration of Secreted Frizzled-Related Proteins (SFRPs) in Non-Small Cell Lung Carcinoma Subtypes-A Preliminary Study.

Non-small cell lung carcinoma (NSCLC) is the most common lung cancer worldwide. Secreted frizzled-related proteins (SFRPs) are important tumour suppressors and antagonists of the Wnt signalling pathway, which is linked with cancer development. The aim of this study was to evaluate the concentrations of SFRP1, SFRP2, and SFRP5 proteins in tumour and non-tumour (NT) samples obtained from 65 patients with primary NSCLC. An enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of SFRPs in the tissue homogenates. A significantly lower SFRP2 protein concentration was found in the total NSCLC tumour samples and the following NSCLC subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (AC) (p > 0.05, p = 0.028 and p = 0.001, respectively). AC tumour samples had a higher SFRP1 level than NT samples (p = 0.022), while the highest SFRP1 concentration was found in NSCLC samples from patients with clinical stage T4 cancer. Increased concentrations of SFRP1 and SFRP5 were present in stage III NSCLC samples, while the tumour samples with high pleural invasion (PL2) had an increased level of SFRP2. The results from this study suggest that the tumour suppressor or oncogenic roles of SFRPs could be connected with the NSCLC subtype. The levels of SFRPs varied according to the clinicopathological parameters of NSCLC.

Cumulative effects of exercise training and consumption of propolis on managing diabetic dyslipidemia in adult women: a single-blind, randomized, controlled trial with pre-post-intervention assessments.

Dyslipidemia is an imbalance of various lipids, and propolis, as a natural resinous viscos mixture made by Apis mellifera L. could improve in this condition. In this single-blind, randomized trial, 60 women with type 2 diabetes and dyslipidemia were divided into four groups: (1) the patients who did not apply the combined training and 500 mg propolis capsules supplement (Control group); (2) subjects performed combined training, including aerobic and resistance training (EXR); (3) subjects received the 500 mg propolis supplement capsules (SUPP); (4) Subjects performed combined training along with receiving the 500 mg propolis supplement capsules (EXR + SUPP). We evaluated the concentration of CTRP12, SFRP5, interleukin-6 (IL6), superoxide dismutase (SOD), malondialdehyde (MDA), adiponectin, and total antioxidant capacity (TAC) before and after the intervention. MDA, TAC, IL6, CTRP12, SFRP5 IL6, adiponectin, and lipid profile levels ameliorated in the EXR + SUPP group. We found that 8 weeks of treatment by combined exercise training and propolis supplement decreased inflammation activity and increased antioxidant defense in women with diabetic dyslipidemia.Trial registration This study was registered in the Iranian Registry of Clinical Trials; IRCT code: IRCT20211229053561N1.

Secreted frizzled-related protein 5: A promising therapeutic target for metabolic diseases via regulation of Wnt signaling.

Metabolic diseases pose a significant global health challenge, characterized by an imbalance in metabolism and resulting in various complications. Secreted frizzled-related protein 5 (SFRP5), an adipokine known for its anti-inflammatory properties, has gained attention as a promising therapeutic target for metabolic diseases. SFRP5 acts as a key regulator in the Wnt signaling pathway, exerting its influence on critical cellular functions including proliferation, differentiation, and migration. Its significance extends to the realm of adipose tissue biology, where it plays a central role in regulating inflammation, insulin resistance, adipogenesis, lipid metabolism, glucose homeostasis, and energy balance. By inhibiting Wnt signaling, SFRP5 facilitates adipocyte growth, promotes lipid accumulation, and contributes to a decrease in oxidative metabolism. Lifestyle interventions and pharmacological treatments have shown promise in increasing SFRP5 levels and protecting against metabolic abnormalities. SFRP5 is a pivotal player in metabolic diseases and presents itself as a promising therapeutic target. An overview of SFRP5 and its involvement in metabolic disorders and metabolism is provided in this comprehensive review. By elucidating these aspects, valuable insights can be gained to foster the development of effective strategies in combating metabolic diseases.

Association of Circulating Plasma Secreted Frizzled-Related Protein 5 (Sfrp5) Levels with Cardiac Function.

Secreted frizzled-related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that may play a role in cardiovascular development and disease. However, there is yet to be a comprehensive investigation into whether circulating SFRP5 can be a biomarker for cardiac function. Plasma SFRP5 levels were measured via ELISA in 262 patients admitted to a cardiology unit. Plasma SFRP5 levels were significantly lower in patients with a history of heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF; p = 0.001). In univariate analyses, SFRP5 levels were also significantly positively correlated with left ventricular ejection fraction (LVEF) (r = 0.52, p < 0.001) and negatively correlated with E/E' (r = -0.30, p < 0.001). Patients with HF, CAD, low LVEF, low triglycerides, high CRP, and high eGFR were associated with lower SFRP5 levels independent of age, BMI, or diabetes after multivariate analysis (overall model r = 0.729, SE = 0.638). Our results show that low plasma SFRP5 levels are independently associated with the presence of HF, CAD, and, importantly, impaired LV function. These results suggest a potential role of SFRP5 as a biomarker, as well as a mediator of cardiac dysfunction independent of obesity and metabolic regulation.

TFAP2C inhibits cell autophagy to alleviate myocardial ischemia/reperfusion injury by regulating miR-23a-5p/SFRP5/Wnt5a axis.

Myocardial ischemia/reperfusion (MI/R) injury contributes to severe injury for cardiomyocytes. In this study, we aimed to explore the underlying mechanism of TFAP2C on cell autophagy in MI/R injury. MTT assay measured cell viability. The cells injury was evaluated by commercial kits. IF detected the level of LC3B. Dual luciferase reporter gene assay, ChIP or RIP assay were performed to verify the interactions between crucial molecules. We found that TFAP2C and SFRP5 expression were decreased while miR-23a-5p and Wnt5a increased in AC16 cells in response to H/R condition. H/R induction led to cell injury and induced autophagy, which were reversed by TFAP2C overexpression or 3-MA treatment (an autophagy inhibitor). Mechanistically, TFAP2C suppressed miR-23a expression through binding to miR-23a promoter, and SFRP5 was a target gene of miR-23a-5p. Moreover, miR-23a-5p overexpression or rapamycin reversed the protective impacts of TFAP2C overexpression on cells injury and autophagy upon H/R condition. In conclusion, TFAP2C inhibited autophagy to improve H/R-induced cells injury by mediating miR-23a-5p/SFRP5/Wnt5a axis.

Pinostrobin induces acute leukemia cell apoptosis via the regulation of miR-410-5p and SFRP5.

AIMS: This study attempted to explore the mechanisms involved in pinostrobin (PN)-mediated acute leukemia cell apoptosis regulated by miR-410-5p. MATERIAL AND METHODS: NB4 and MOLT-4 cells were cultured and treated with PN at the IC50 concentration. Apoptosis was examined by Annexin V-FITC/PI staining. RT-qPCR was used to measure the expression of caspase-3, BAK, BCL-W, and MCL-1. The target protein of PN was identified using LC-MS/MS followed by bioinformatic analysis. TargetScan, DIANA, and miRDB were used for the prediction of miRNAs involved in the PN-induced apoptosis mechanism. miRNA mimic transfection, RT-qPCR, and western blot analysis were performed to evaluate the regulatory effect of miRNA on its target and the involvement of miRNA in apoptosis induction by PN. In addition, the synergistic effect of PN and daunorubicin (DNR) were investigated by using the MTT assay. KEY FINDINGS: The results showed that PN reduced cell viability and induced apoptosis in both leukemia cell lines. From the LC-MS/MS and bioinformatics analysis, SFRP5 and miR-410-5p were selected as a potential PN target protein and miRNA, respectively. After miRNA mimic transfection, miR-410-5p, which is an onco-miRNA, was decreased and led to increased apoptosis in both cell lines, indicating that this miRNA is involved in PN-mediated apoptosis mechanisms. Moreover, PN demonstrated a synergistic effect with DNR, suggesting that PN may be used in combination with conventional chemotherapy drugs. SIGNIFICANCE: PN regulates the expression of miR-410-5p and SFRP5 to promote apoptosis in acute leukemia cells. It could be developed as an alternative treatment for leukemia in the future.

Frizzled receptors and SFRP5 in lipid metabolism: Current findings and potential applications.

Lipid metabolism plays a very important role as the central metabolic process of the body. Lipid metabolism interruptions may cause many chronic diseases, for example, non-alcoholic fatty liver disease (NAFLD), diabetes, and obesity. Secreted Frizzled Related Protein 5 (SFRP5) and Frizzled receptors (FZD) are two newly discovered adipokines that are involved in lipid metabolism as well as lipogenesis. Both of these adipokines affect lipid metabolism and adipogenesis through three WNT signaling pathways (WNTSP): WNT/ß-catenin, WNT/Ca2+, and WNT/JNK. FZD consists of 10 species, which have a cysteine-rich domain (CRD) to bind to the WNT protein for signal transduction. Depending on the type of ligand or co-receptor, they can stimulate or inhibit adipogenesis. In lipid metabolism, they play a role in recognizing fatty acids. In obesity, gene expression of the WNT/FZD receptors is significantly increased. In contrast, SFPR5 serves as an antagonist that can compete with FZD for inhibition of WNTSP. It is believed to have anti-inflammatory potential in obesity and diseases related to abnormal lipid metabolism. In these cases, the expression of SFRP5 is found to be very low leading to the promoted production of proinflammatory cytokines (PICS). Some methods that include using recombinant SFRP5 to improve non-alcoholic steatohepatitis (NASH), using secreted Ly-6/uPAR-related protein 1 (Slurp1) to regulate fat accumulation in the liver through SFRP5, and dietary and lifestyle interventions to improve overweight/obesity have been studied. However, understandings of the molecular mechanisms of these two adipokines and their interactions are very limited. Therefore, more in-depth studies are needed in the future.

Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome.

Our study focused on investigating the clinical significance of serum Sfrp5/Wnt-5a levels as a risk marker in metabolic syndrome (MetS). The study involved a total of 107 treatment-naive MetS cases and 100 controls with similar age and sex belonging to northern India. The profiling of clinical, biochemical, and anthropometric variables was done. ELISA methods were employed for serum cytokine estimation. Serum Sfrp5 was inversely correlated with BMI, WC, SBP, DBP, FPG, TG, fasting insulin level, and HOMA-IR in both males and females. The best cutoff value for Sfrp5 to predict MetS in males was ≤40.48 ng/ml (sensitivity 53.70% and specificity 90.48%), while in female, it was ≤66.67 ng/ml (sensitivity 98.11% and specificity 34.48%). MetS occurrence decreased with increasing concentration of Sfrp5 with an odds ratio (OR) of 0.95 (95% CI = 0.92-0.98, P < .001) in male and 0.93 (95% CI = 0.91-0.97, P < .001) in female. Quartile analysis revealed that odds of MetS significantly decreased in quartile 4 vs. 1, 0.06 (95% CI = 0.01-0.25), P = .001 and 0.13 (95% CI = 0.04-0.44), P = .001, respectively, in male and female. The inverse association of serum concentration of Sfrp5 with MetS might have a useful addition to the available risk marker as well as a therapeutic target for MetS.

The effects of exercise training induced calories expenditure on type 2 diabetes related cardio metabolic physiological parameters and adipocytokines.

Background: Recently, many studies have examined the effects of various training on pro-inflammatory and anti-inflammatory adipocytes. The results of these studies are contradictory. Some have reported positive effects and others have reported negative effects. However, there is no research to study the effect of exercise on similar energy expenditures on adipocytes. Hence the purpose of this study was the effects exercise training induced calories expenditure on type 2 diabetes related cardio metabolic physiological parameters and adipocytokines. Methods: Sixty-eight men patients with type 2 diabetes [12 weeks] were randomized to 4 groups according to training regimens. the groups are [1] HIIT [n = 17], [2] RT[n = 17], [3] AT[n = 18], and [4] AT + RT n = 16]. For 12 weeks [4 days/week, 20-30 min/season], participants performed training sessions with 300 kcal energy expenditure. Before and after 12 weeks interventions, Anthropometric and physiological variables and Glucose, insulin, FFA, LDL, HDL, TG, TC collected and analyses. Leptin, SFRP5, LGR4 and Irisin levels in Serum were assessment by ELISA. Results: Serum irisin concentrations were significantly higher in AT [%20.4] compared to other groups. Leptin, SFRP5 and LGR4 were significantly higher in HIIT [%-21.7, %48.1 and %30.9 respectively] compared to other groups. Serum SFRP5 concentrations were significantly increased in 4 groups[P > 0.05]. However, leptin and LGR4 were significantly decreased and increased in 3 groups expect in RT group[P > 0.05]. And irisin concentrations were significantly increased in AT group only[P > 0.05]. And many variables indicated positive and negative relationship between together [P > 0.05]. Conclusions: The findings of the present study showed that if exercised with energy expenditure equal to HIIT training, it has the greatest effect on improving inflammatory and anti-inflammatory indicators in type 2 diabetic patients, as well as glycemic and lipid-chemical variables.

Secreted frizzled-related protein 5 promotes angiogenesis of human umbilical vein endothelial cells and alleviates myocardial injury in diabetic mice with myocardial infarction by inhibiting Wnt5a/JNK signaling.

The purpose of this study is to investigate whether secreted frizzled-related protein 5 (SFRP5) affects the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) induced by high glucose (HG). HUVECs were treated with different concentrations of glucose. MTT, wound healing, angiogenesis, and ELISA assays were used to detect cell cytotoxicity, migration, tube formation, and VEGF165 and VEGF165b levels, respectively. The mice model of type 2 diabetes mellitus (T2DM) complicated with myocardial infarction (MI) was established. SFRP5 was injected intrabitoneally for 2 weeks. cardiac output (CO), left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected by echocardiography. Western blot was used to detect the protein levels of SFRP5, Wnt5a, JNK1/2/3, p-JNK1/2/3, TGF-ß1, Caspase3, Bax, and Bcl-2. The expression of SFRP5 was declined in HG-induced HUVECs and T2DM-MI. Intervention of SFRP5 promoted the migration of HUVECs and angiogenesis, as evidenced by a lower expression of Bax and caspase3, but a higher expression of Bcl-2. Meanwhile, SFRP5 inhibition repress Wnt5a and p-JNK expression. Howerver, The JNK inhibitor (SP600125) enhanced the down-regulation of Wnt5a/JNK pathway proteins by SFRP5. SFRP5 intervention increased the levels of CO, LVSF, and LVEF in T2DM-MI mice. SFRP5 inhibited myocardial pathological injury and fibrosis in T2DM-MI mice and SFRP5 could down-regulate Wnt5a and p-JNK1/2/3 activation. SFRP5 promotes the proliferation, migration and angiogenesis of HUVECs induced by HG, and inhibits cardiac dysfunction, pathological damage, fibrosis, and myocardial angiogenesis in diabetic myocardial ischemia mice, which is achieved by inhibiting Wnt5a/JNK signaling.