Silymarin is known for its anti-inflammatory and antioxidant properties. We investigated these effects on serum levels of CTRP3, Anti-CCP, and hs-CRP in individuals with Rheumatoid arthritis (RA). In this study, 42 individuals with RA were recruited and their serum specimens were collected, serum levels of hs-CRP, AntiCCP antibodies, and CTRP3 were measured using ELISA. DNA was extracted and investigated for the existence of possible new mutations in the gene encoding CTRP3 using the PCR technique; the desired fragments were then amplified and sequenced. Another blood sample was collected from the case group after taking livergol for three months (3 doses of 140 mg/day) and the tests were repeated. Anti-CCP Abs levels in the postintervention responding group decreased compared to preintervention (p<0.001) while in the non-responding group, the levels increased after the intervention compared to the levels before the intervention (p=0.019). Additionally, CTRP3 levels in the responding group increased postintervention (p=0.003), however, in the non-responding group the levels decreased postintervention when compared to preintervention (p=0.02). The responding group had significantly lower levels of hs-CRP when compared to that of preintervention (p=0.005) whereas the non-responding group had significantly higher levels of postintervention (p<0.001). Moreover, the results of sequencings of exon 6 on CTRP3 gene showed the presence of mutations in exon 6 (position 215:C>T, 338:G>A, 359:A>C, and 153:T>C). Silymarin could be used as an adjuvant in the treatment of rheumatoid arthritis.

BACKGROUND: Cardiac hypertrophy can be a pathological process that impairs heart function. Anthocyanins are a well-characterized type of natural antioxidant, and recent studies have shown that this type of compound has potential cardioprotective effects against different disorders, such as cardiac hypertrophy.
OBJECTIVE: We assessed the anti-hypertrophy potential of cyanidin-3-O-glucoside (C3G) and the mechanism associated with any observed effects.
METHODS: Hypertrophy symptoms were induced using the transverse aortic constriction (TAC) operation in vivo and angiotensin II (Ang II) in vitro. The effect of C3G on the development of hypertrophic symptoms was then determined. Moreover, we examined the influence of CTRP3 inhibition on the anti-hypertrophy function of C3G.
RESULTS: The TAC operation induced cardiac fibrosis and heart weight increase, which was associated with increased production of cytokines and suppressed activity of the CTRP3/AMPK pathway. The impairments of heart structure and function were attenuated by C3G. Angiotensin II induced size increases of neonatal rat cardiomyocytes (NRCMs) in vitro, and this effect was inhibited by C3G. Furthermore, the inhibition of CTRP3 counteracted the function of C3G by promoting NRCM hyperplasia and inflammation.
CONCLUSIONS: The results of the current study showed that the activation of CTRP3 contributed to the anti-hypertrophy effects of C3G.

BACKGROUND: The study aimed to investigate novel biomarkers from the C1q TNF superfamily and evaluate their role in autoimmune inflammatory rheumatic diseases with the goal of identifying an effective biomarker to measure clinical disease activity and assess treatment efficacy.
METHODS: Sixty-one Axial spondyloarthritis (AxSpa) patients and 30 healthy controls were enrolled in the study. The serum biomarkers subfatin, CTHRC1, CTRP3, CTRP6, IL-6, IL-17, and TNF-α and the disease indices BASDAI, BASFI, MASES, and ASDAS-ESR/CRP were evaluated and compared. The patients were then classified, and their serum biomarkers were assessed according to their ASDAS scores and their treatment regimens.
RESULTS: Among the studied biomarkers, none showed a significant difference between the patients and the healthy controls. Although the difference was not statistically significant, the median values of serum subfatin, CTHRC1, CTRP3, CTRP6, IL-6, IL-17, and TNF-α were all found to be lower in the AxSpa patients than in the healthy controls. Furthermore, once the patients were classified regarding their disease activity, no correlation between the study biomarkers and levels of clinical disease indices was observed. Finally, biological treatments were found to affect the serum concentration of these biomarkers regardless of the level of disease activity.
CONCLUSIONS: Novel adipokines and known modulators of inflammation, circulating subfatin, CTHRC1, CTRP3, CTRP6, IL-6, IL-17, and TNF-α levels may play a role in assessing treatment efficacy, especially in those treated with TNF-inhibitors. However, we failed to demonstrate a correlation between clinical disease activity and serum biomarker levels.

Cisplatin has been widely studied and found to be a highly effective anti-tumor drug. It has several side effects, including acute kidney injury (AKI). Cisplatin-induced AKI can be primarily attributed to oxidative stress, inflammation, and apoptosis. The CTRP3 adipokine is a new adipokine that exhibits antioxidant, anti-inflammatory, and antiapoptotic properties. Despite this, the role of CTRP3 in AKI remain unclear. In cisplatin-induced AKI models, our findings demonstrated that CTRP3 expression was decreased in human proximal tubule epithelial cells (HK-2). In the in vitro experiments, HK-2 cells were first transfected with an overexpression plasmid of CTRP3 (pcDNA-CTRP3) or a small interfering RNA for CTRP3 (si-CTRP3) and induced by cisplatin; and cell oxidative stress, inflammation, proliferation, and apoptosis were found to be present. Overexpressing CTRP3 inhibited oxidative stress through decreasing malondialdehyde (MDA) levels and increasing the activity of SOD and CAT. The mRNA levels of SOD1 and SOD2 were increased in response to CTRP3 overexpression. Additionally, CTRP3 decreased TNF-α and MCP-1 levels. Moreover, CTRP3 overexpression increased cisplatin-induced cell activity and decreased cell apoptosis, as indicated by the elevated numbers of EdU positive cells and decreased numbers of apoptotic cells. Consistent with these results, the overexpression of CTRP3 effectively elevated the mRNA levels of Bcl-2 and reduced the mRNA levels of Bax. In contrast, inhibition of CTRP3 expression by si-CTRP3 reversed the cisplatin-induced indices. Mechanistically, we found that the overexpression of CTRP3 can increase expression of Nrf2 and inhibit the activation of MAPK phosphorylation (ERK, JNK, and p38). Furthermore, inhibition of ERK, JNK and p38 activity eliminated aggravation of cisplatin-induced inflammation and apoptosis caused by CTRP3 knockdown. Additionally, the cisplatin-induced oxidative stress and activation of MAPK phosphorylation (ERK, JNK, and p38) in HK-2 cells were reversed by Nrf2 suppression by siRNA. Collectively, these results indicated that CTRP3 may identify as a novel target for AKI treatment and protect against cisplatin-induced AKI through the Nrf2/MAPK pathway.

BACKGROUND: Asthma is a common illness with chronic airway inflammation. C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) plays a vital role ininflammatory response, but its effect on asthma is imprecise. Herein, we analyzed the functions of CTRP3 in asthma.
METHODS: The BALB/c mice were randomized into four groups: control, ovalbumin (OVA), OVA+vector, and OVA+CTRP3. The asthmatic mice model was established by OVA stimulation. Overexpression of CTRP3 was implemented by the transfection of corresponding adeno-associated virus 6 (AAV6). The contents of CTRP3, E-cadherin, N-cadherin, smooth muscle alpha-actin (α-SMA), phosphorylated (p)-p65/p65, transforming growth factor-beta 1 (TGFβ1), and p-Smad3/Smad3 were determined by Western blot analysis. The quantity of total cells, eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage fluid (BALF) was assessed by using a hemocytometer. The contents of tumor necrosis factor-α and interleukin-1β in BALF were examined by enzyme-linked immunesorbent serologic assay. The lung function indicators and airway resistance (AWR) were measured. The bronchial and alveolar structures were evaluated by hematoxylin and eosin staining and sirius red staining.
RESULTS: The CTRP3 was downregulated in mice of OVA groups; however, AAV6-CTRP3 treatment markedly upregulated the expression of CTRP3. Upregulation of CTRP3 diminished asthmatic airway inflammation by decreasing the number of inflammatory cells and the contents of proinflammatory factors. CTRP3 markedly lessened AWR and improved lung function in OVA-stimulated mice. Histological analysis found that CTRP3 alleviated OVA-induced airway remodeling in mice. Moreover, CTRP3 modulated NF-κB and TGFβ1/Smad3 pathways in OVA-stimulated mice.
CONCLUSIONS: CTRP3 alleviated airway inflammation and remodeling in OVA-induced asthmatic mice via regulating NF-κB and TGFβ1/Smad3 pathways.

UNASSIGNED: To assess serum 25-hydroxyvitamin D3 (25(OH)D3), fibroblast growth factor 23 (FGF23), and C1q/tumor necrosis factor-related protein-3 (CTRP3) levels in nondialysis chronic kidney disease (CKD) patients and their relationship with coronary artery calcification (CAC).
UNASSIGNED: One hundred and twenty-eight patients diagnosed with CKD were selected and all underwent cardiac computed tomography. CAC was assessed using the Agatston score, and coronary artery calcification score (CACs) >10 was identified as CAC. The differences in serum 25(OH)D3, FGF23, and CTRP3 levels between the CAC and non-CAC groups were analyzed. Their correlation with CACs was assessed by Spearman\'s analysis, and logistic regression analysis was used to find risk factors for CAC.
UNASSIGNED: Compared to the non-CAC group, the CAC group was older (64.21 ± 9.68 years), with a higher percentage of hypertension (93.10%) and diabetes (63.80%) and higher levels of serum CTRP3 [1079.20 (644.4-1567.2) ng/mL]. However, there was no significant difference in serum 25(OH)D3 and FGF23 between these two groups. The high level CTRP3 group had a higher prevalence of CAC (61.5%). Logistic regression results showed that age, diabetes, decreased 25(OH)D3 (odds ratio (OR) = 0.95, p = .030) and high levels of CTRP3 (OR = 3.19, p = .022) were risk factors for CAC in nondialysis CKD patients.
UNASSIGNED: Serum CTRP3 levels progressively increased with the progression of kidney disease, while 25(OH)D3 levels progressively decreased. Decreased 25(OH)D3 and high levels of CTRP3 are associated with CAC in patients with nondialysis CKD.

Ischemic stroke seriously endangers human health and even death. This study aimed to investigate the role of KLF10/CTRP3 in oxygen-glucose deprivation/reperfusion (OGD/R)-induced brain microvascular endothelial cells injury, as well as the regulatory effects of the Nrf2/HO-1 signaling pathway. OGD/R-induced human microvascular endothelial cells (hBMECs) were used to simulate the model of cerebral ischemia-reperfusion (I/R) injury. The expression of KLF10/CTRP3 in OGD/R-induced hBMECs as well as the transfection efficiency were all detected by RT-qPCR and western blot. The interaction of KLF10 and CTRP3 was confirmed by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP). The viability, apoptosis and endothelial permeability of OGD/R-induced hBMECs was detected by CCK-8, TUNEL and FITC-Dextran assay kit. The capacity of cell migration was assessed by wound healing assay. The expression of apoptosis related proteins, oxidative stress levels and tight junction proteins was also detected. As a result, the expression of KLF10 was increased in OGD/R-induced hBMECs and downregulation of KLF10 could promote the viability, migration and suppress the apoptosis, oxidative stress and endothelial permeability by downregulating the expression of caspase 3, Bax, cleaved PARP, ROS, MDA, and upregulating the expression of Bcl-2, SOD, GSH-Px, ZO-1, occludin, claudin-5. Nrf2/HO-1 signaling pathway was inhibited in OGD/R-induced hBMECs, which was activated by downregulation of KLF10. KLF10 was demonstrated to be combined with CTRP3 and KLF10 inhibited transcription of CTRP3 in hBMECs. The above changes affected by downregulation of KLF10 could be reversed by the interference with CTRP3. In conclusion, KLF10 knockdown improved OGD/R-induced brain microvascular endothelial cell injury and barrier dysfunction through the activation of Nrf2/HO-1 signaling pathway, which was weakened by the downregulation of CTRP3.

BACKGROUND: C1q/TNF-related protein 3 (CTRP3) has been clarified to display its protective roles in cardiac function. The current study is concentrated on exploring the impacts of CTRP3 on myocardial ischaemia.
METHODS: Oxygen and glucose hypoxia/reoxygenation (OGD/R) model was constructed in human cardiac microvascular endothelial cells (HCMECs). Reverse transcription-quantitative polymerase chain reaction and western blot analysis of CTRP3 expression were conducted. CCK-8 assay was to estimate cell activity and lactate dehydrogenase (LDH) assay kit was to test LDH release. TUNEL assay and western blot were to judge apoptosis. Endothelial barrier function was detected by in vitro vascular permeability assay kit. Zonula occludens-1 (ZO-1) expression was evaluated by immunofluorescence assay. The interaction between CTRP3 promoter and Forkhead Box O6 (FOXO6) was predicted by JASPAR database and verified by chromatin immunoprecipitation and luciferase reporter assays. After OGD/R-induced HCMECs were co-transfected with CTRP3 overexpression and FOXO6 overexpression plasmids, the above functional experiments above were conducted again. Lastly, the expression of sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling-related proteins was examined by western blot.
RESULTS: CTRP3 was down-regulated in OGD/R-induced HCMECs. CTRP3 enhanced the viability and barrier integrity while reduced the apoptosis and permeability of OGD/R-insulted HCMECs. This process may be regulated by FOXO6 transcription. Also, FOXO6 inhibition-mediated CTRP3 up-regulation activated the SIRT1/Nrf2 signalling.
CONCLUSIONS: FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling.

OBJECTIVE: Obesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression.
METHODS: Patients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered).
RESULTS: 81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1±23.8 vs 84.5±6.2; p=0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4±24.7 vs 106±24.7;p<0.01). During a mean follow-up of 68 months, 15 patients had a renal event. Patients in the higher CTRP3 tertile had less events but without statistical significance (p=0.07). Obese patients in the higher CTRP3 tertile significantly had less renal events (p=0.049). By multiple regression analysis CTRP3 levels could not predict renal events (HR 0.98; CI95% 0.96-1.06).
CONCLUSIONS: CTRP3 levels are higher in woman than men in patients with CKD, with similar levels between obese and non obese. Higher CTRP3 levels at baseline were associated with better renal outcomes in obese patients.

OBJECTIVE: Gestational diabetes mellitus (GDM) is closely related to obesity, adipose tissue, and adipokines. Adiponectin-homologous adipokines with anti-inflammatory properties, including C1q/TNF-related protein 3 (CTRP3) and CTRP9, regulate glucose and lipid metabolism, which was measured in pregnant women with GDM with the aim to assess their circulating levels and their relation with inflammatory cytokines and other biochemical data.
METHODS: Serum levels of CTRP3, CTRP9, adiponectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured in 43 subjects with GDM and 42 healthy controls by enzyme-linked immunosorbent assay.
RESULTS: Serum levels of adiponectin and CTRP3 were lower in GDM subjects than in controls, whereas CTRP9, TNF-α, and IL-6 showed higher concentrations in subjects with GDM than in controls. In the subjects with GDM, there was a significant association of CTRP3 with homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, and triglycerides, whereas CTRP9 is associated with TNF-α and HOMA-IR.
CONCLUSIONS: The differences in the assessed levels of CTRP3 and CTRP9 suggest a possible relation with the pathogenesis of GDM, in particular insulin resistance, which showed significant association with both adipokines.