High glucose combined with high FFAs can contribute to the unfavorable development of type 2 diabetes mellitus (T2DM) and monocytes/macrophages are important in the occurrence and development of T2DM, which is regarded as a type of low‑grade inflammation. Although our previous study demonstrated that increased expression of P2X7 receptor (P2X7R) in peripheral blood monocytes may alter the innate immune system and that long non‑coding (lnc)RNA uc.48+ was involved in diabetic neuropathic pain, the involvement of uc.48+ mediated by the P2X7R in monocyte/macrophages during T2DM has not been reported. In the present study, the effectsof uc.48+ small interference RNA (siRNA) on factors, including the mRNA and protein expression of P2X7R, apoptosis and proliferation, levels of reactive oxygen species (ROS), cytokine levels, and expression of phosphorylated (p‑) extracellular signal‑regulated kinase (ERK)1/2, were examined in RAW264.7 macrophages following exposure to high glucose and high plasma free fatty acids (FFAs). After RAW264.7 cells were transfected with uc.48+ siRNA under high glucose conditions and FFAs treatment, the mRNA expression levels of uc.48+ and P2X7 receptor were detected by reverse transcription‑polymerase chain reaction. The protein mass of P2X7 receptor and ERK signaling pathway were assessed by western blotting. ROS and calcium concentrations, and culture supernatant cytokine content [tumor necrosis factor‑α, interleukin (IL)‑10, IL‑1β] were detected by fluorescent probes and ELISA respectively. Cell viability and apoptosis were determined by MTS test and flow cytometry, respectively. It was found that treatment of RAW264.7 cells with high glucose and FFAs, which exhibited increased expression of uc.48+, evoked P2X7R‑mediated immune and inflammatory responses through several means, including cytokine secretion, ROS formation, and activation of the ERK signaling pathway. The uc.48+ siRNA regulated these factors and thus influenced the course and outcome of the immune and inflammatory responses mediated by P2X7R.

BackgroundSerum prealbumin (PA), which is a nutritional index, has been found to be associated with severities and prognoses of various diseases. However, there are no reports about the relationship between PA and angiographic severity of coronary artery disease.Material/MethodsThis cross-sectional study included 867 patients with acute coronary syndrome (ACS) who underwent coronary angiography. Patients were divided into quartiles of PA and coronary artery stenosis was determined by angiographic Gensini score, the presence of high Gensini score (Gensini score ≥120), and triple-vessel disease. Multivariate linear and logistic regression analyses were performed to explore the relationship between PA and disease severity in a coronary angiogram.ResultsThere was a significant and independent negative correlation between PA and Gensini score in multivariate linear regression (p=0.015). Logistic regression analysis revealed that crude odds ratios of triple-vessel disease and high Gensini score were 2.47 (95% CI: 1.66–3.67) and 1.83 (95% CI: 1.50–3.49), respectively, in the first quartile of PA compared with the fourth quartile and the results remained significant for high Gensini score after adjustment for confounding factors. In addition, estimated glomerular filtration rate, liver function, and high-sensitivity C-reactive protein (hs-CRP) had no interactive relationships in the above associations. Patients with lower levels of albumin or higher levels of hs-CRP or the ratio of hs-CRP to PA (hs-CRP/PA) also had more severe coronary atherosclerosis.ConclusionsPA is negatively and independently associated with angiographic severity in patients with ACS, indicating for potential use in estimating the burden of coronary atherosclerosis.

of detection) did not identify an aberrant clonal plasma cell population in this patient.We conclude that for select patients with clinical features of systemic AL amyloidosis (ie, heart failure with preserved ejection fraction, proteinuria, unexplained hepatomegaly, and axonal demyelinating peripheral neuropathy), the absence of monoclonal gammopathy should not deter aspiration of subcutaneous fat and/or tissue biopsy of the affected organ. Only histopathological analysis for Congophilia and accurate precursor protein typing can lead to diagnosis in some cases. Moreover, it is important to distinguish these systemic cases from localized AL amyloidosis, which does not require systemic chemotherapy.The authors declare no competing conflicts of interest. AUTHOR CONTRIBUTIONSAS collected and analyzed data, and wrote the manuscript in consultation with YK, DJM and JMS; VS edited and revised the final version.

Cardiomyocytes hypertrophy and apoptosis induced by advanced glycation end products (AGEs) is the crucial pathological foundation contributing to the onset and development of diabetic cardiomyopathy (DCM). However, the mechanism remains poorly understood. Here, we report that profilin-1 (PFN-1), a well-known actin-binding protein, serves as a potent regulator in AGEs-induced cardiomyocytes hypertrophy and apoptosis. PFN-1 was upregulated in AGEs-treated H9c2 cells, which was associated with increased cardiomyocytes hypertrophy and apoptosis. Silencing PFN-1 expression remarkably attenuated AGEs-induced H9c2 cell hypertrophy and apoptosis. Mechanistically, AGEs increased PFN-1 expression through elevating ROS production and RhoA and ROCK2 expression. Consequently, elevated PFN-1 promoted actin cytoskeleton disorganization. When either ROS production/ROCK activation was blocked or cells were treated with Cytochalasin D (actin depolymerizer), H9c2 cells were protected against AGEs-induced cardiac myocyte abnormalities, concomitantly with downregulated expression of PFN-1 and improved actin cytoskeleton alteration. Collectively, these data suggest that PFN-1 may play an important role in AGEs-induced hypertrophy and apoptosis in H9c2 cells.

Cardiac injury, including hypertrophy and fibrosis, induced by advanced glycation end products (AGEs) has an important function in the onset and development of diabetic cardiomyopathy. Profilin-1, a ubiquitously expressed and multifunctional actin-binding protein, has been reported to be an important mediator in cardiac hypertrophy and fibrosis. However, whether profilin-1 is involved in AGE-induced cardiac hypertrophy and fibrosis remains to be determined. Therefore, the present study aimed to investigate the function of profilin-1 in cardiac injury induced by AGEs. The model of cardiac injury was established by chronic tail vein injection of AGEs (50 mg/kg/day for 8 weeks) in Sprague-Dawley rats. Rats were randomly assigned to control, AGEs, AGEs + profilin-1 shRNA adenovirus vectors (AGEs + S)or AGEs + control adenovirus vectors (AGEs + V) groups. Profilin-1 shRNA adenovirus vectors were injected via the tail vein to knockdown profilin-1 expression at a dose of 3×109 plaque forming units every 4 weeks. Echocardiography was performed to measure cardiac contractile function. Cardiac tissues were stained with Masson's trichrome stain to evaluate ventricular remodeling. The serum levels of procollagen type III N-terminal peptide were detected by ELISA. The expression of profilin-1, receptor for AGEs (RAGE), Rho, p65, atrial natriuretic peptide, β-myosin heavy chain, matrix metalloproteinase (MMP)-2 and MMP-9 were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and/or western blot analysis and immunohistochemistry staining. The results demonstrated that chronic injection of exogenous AGEs led to cardiac dysfunction, hypertrophy and fibrosis, as determined by echocardiography, Masson trichrome staining and the expression of associated genes. The expression of profilin-1 was markedly increased in heart tissue at the mRNA and protein level following AGE administration, as determined by RT-qPCR and western blotting, which was further confirmed by immunohistochemistry staining. Furthermore, the expression of RAGE, Rho and p65 was also increased at the protein level. Notably, knockdown of profilin-1 expression ameliorated AGE-induced cardiac injury and reduced the expression of RAGE, Rho and p65. These results indicate an important role for profilin-1 in AGE-induced cardiac injury, which may provide a novel therapeutic target for patients with diabetic heart failure.

To analyze the clinical, serological, and imaging characteristics of patients with interstitial lung diseases (ILD) positive to different anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies. The clinical data, serological indexes, pulmonary high-resolution computed tomography (HRCT) imaging features and pulmonary functions, and bronchoalveolar lavage fluid of 84 ILD patients with anti-ARS antibody positive in Beijing Chao-yang Hospital, Capital Medical University were reviewed. (1) Anti-ARS antibodies included anti-Jo-1 (42.86%), anti-PL-7 (26.19%), anti-PL-12 (10.71%), anti-EJ (14.29%), and anti-OJ (5.95%). (2) Nonspecific interstitial pneumonia was the main type of patients with ILD positive to antibodies of anti-Jo-1, anti-PL-7, and anti-EJ, organizing pneumonia was the main type of patients with ILD positive to anti-PL-12 antibody and usual interstitial pneumonia was the main type of patients with ILD positive to anti-OJ antibody. (3) Only 14.29% of the patients had typical “triad syndrome” (interstitial pneumonia, myositis, and non-erosive arthritis). Myositis mainly occurred in patients with ILD positive to antibodies of anti-PL-7, anti-Jo-1, and anti-EJ. The incidence of arthritis in ILD patients with anti-Jo-1 was higher than that in ILD patients with anti-PL-12 and anti-EJ ( P < .05). The incidence of mechanic's hand in ILD patients with anti-Jo-1 was higher than that in ILD patients with anti-PL-12 ( P < .05). ILD positive to anti-Jo-1 antibody is associated with multiple organ involvement, mainly manifested as myositis, mechanic's hand, and arthritis. As other clinical manifestations of some ILD patients are relatively hidden, ILD patients should pay attention to the screening of the anti-ARS antibodies and guard against anti-synthetase syndrome.

ObjectivesRheumatoid arthritis (RA) is a disabling disease with a high incidence that is regularly accompanied by cardiovascular complications. Several studies have suggested that renin–angiotensin–aldosterone system (RAAS) is closely associated with RA. The aim of this study was to investigate the mechanisms underlying Angiotensin-(1–7) [Ang-(1–7)] and its Mas receptor agonist (AVE0991) on joint inflammation and cardiac complications in a collagen-induced arthritis (CIA) model.MethodsCollagen type II was injected into DBA/1 mice to construct an arthritis model. CIA mice were treated with Ang-(1–7) (2.0 mg/kg intraperitoneally) and AVE0991 (3.0 mg/kg intraperitoneally). The serum levels of inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 β, IL-6, and C-reactive protein (CRP)] were determined by ELISA. The mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways in joint tissues and the transforming growth factor (TGF)-β/Smad pathway and levels of α-Smooth muscle action (SMA) and β-myosin heavy chain (MHC) protein expression in cardiac tissues were assessed by western blots. The levels of TGF-β/Smad pathway, α-SMA, and β-MHC RNA in cardiac tissues were analyzed by real time-PCR. The levels of receptor activator of nuclear factor kappa ligand (RANKL) and promoting matrix metalloproteinase (MMP)-3 expression in the ankle joints were detected by immunohistochemistry and real time-PCR.ResultsAng-(1–7) and AVE0991 reduced the levels of inflammatory cytokines and inhibited the MAPKs and NF-κB signaling pathways in ankle joint tissues, reduced RANKL and MMP3 expression, and ameliorated local joint inflammation and bone destruction compared with the control group. In addition, Ang-(1–7) and AVE0991 attenuated the TGF-β/Smad signaling pathway, reduced the levels of α-SMA and β-MHC expression, and diminished inflammatory cell infiltration into the myocardial interstitium and myocardial interstitial fibrosis in the hearts of CIA mice.ConclusionsAng-(1–7) alleviated joint damage caused by inflammation likely through the attenuation of NF-κB and MAPK pathways and ameliorated inflammation-induced cardiac fibrosis and activation of the TGF-β/Smad pathway. Moreover, Ang-(1–7) was likely mediated through the Mas receptor. This study provides theoretical evidence for exploring novel clinical therapeutic approaches for RA and its cardiac complications.

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