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Obesity is a major global health concern and induces numerous complications, such as heart and kidney injury. Inflammation is an important pathogenic mechanism underlying obesity‑associated tissue injury. (1E,4E)‑1‑{2,4‑Dimethoxy‑6‑[(E)‑4‑methoxystyryl]phenyl}‑5‑​(2,4‑dimethoxyphenyl)penta‑1,4‑dien‑3‑one (PA19) is a novel anti‑inflammatory compound synthesized by our research group. In the present study, the efficacy of PA19 in attenuating high‑fat diet (HFD)‑induced heart and kidney injury was investigated. Heart and kidney pathological injury and fibrosis were detected by hematoxylin and eosin and Sirius red staining, respectively. The expression levels of inflammatory genes and fibrosis‑associated protein were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. ELISA was used to detect the level of inflammatory cytokines. Following 20 weeks of HFD treatment, mice exhibited increased lipid accumulation in the serum, heart and kidney injury and fibrosis, and inflammation and inflammatory cell infiltration compared with mice fed a control diet. Conversely, treatment with PA19 during the final 12 weeks of the study significantly reduced the degree of heart and kidney fibrosis and inflammation induced by HFD. The results suggested that PA19 attenuates heart and kidney inflammation and injury induced by HFD, and indicated that PA19 may be a novel therapeutic agent in the treatment of obesity, and obesity‑induced cardiac and renal injury.

Oxymatrine (OMT), which is a quinolizidine alkaloid extracted from the traditional Chinese herb Sophora flavescens Aiton, is often used to treat various inflammatory diseases. The present study aimed to investigate the protective effects of OMT against septic shock‑induced myocardial injury in rats, and to determine the underlying mechanisms. In the present study, cecal ligation and puncture (CLP) was applied to generate a rat model of sepsis. The rats were randomly divided into six groups (n=8/group): Sham operation (CON) group, OMT control group, CLP model group, and CLP + OMT (high dose, 52 mg/kg; medium dose, 26 mg/kg; low dose, 13 mg/kg) groups. Cardiac function and histological alterations were analyzed by light microscopy and electron microscopy. Myocardial cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mRNA and protein expression levels were examined by reverse transcription-polymerase chain reaction and western blotting, respectively. Furthermore, the levels of tumor necrosis factor (TNF)‑α in the myocardial tissue were determined by radioimmunoassay. The results demonstrated that OMT exhibited anti‑inflammatory properties, improved myocardial contractility and compliance, and significantly decreased pathological injury to rat myocardial ultrastructure. In addition, OMT significantly decreased heart rate and left ventricular end diastolic pressure, and increased mean arterial pressure, left intraventricular pressure change rate, and left ventricular end systolic pressure in rats following septic shock. Treatment with OMT attenuated the mRNA expression of lipopolysaccharide binding protein, cluster of differentiation 14, nuclear factor (NF)‑κB (p65), TNF‑α, p38‑mitogen‑activated protein kinase (MAPK) and caspase‑3, and decreased the protein expression of NF‑κB (p65), phosphorylated (p) NF‑κB inhibitor‑α, p‑p38‑MAPK caspase‑3 and TNF‑α in septic myocardial tissue. The present study concluded that OMT may offer substantial therapeutic potential for the treatment of septic shock‑induced myocardial injury by inhibiting the TNF-α/p38-MAPK/caspase-3 signaling pathway.

Secreted frizzled-related protein 5 (SFRP5) is one of the anti-inflammatory adipokines secreted from white adipose tissue. However, little is known about the effect of SFRP5 on the cardiovascular system. The aim of the present study was to determine the effect of SFRP5 on smooth muscle cell (SMC) proliferation, migration and inflammation. The plasma levels of SFRP5 were evaluated in a cohort‑based elderly population using ELISA, and the expression of SFRP5 in Sprague‑Dawley rat aortas was detected using immunohistochemistry. SMC proliferation and migration were evaluated in vitro using 5‑ethynyl‑2'‑deoxyuridine cell proliferation and wound‑healing assays, respectively, while reactive oxygen species (ROS) production and cell signaling were assessed using a 2',7'‑dichlorodihydrofluorescein diacetate assay and immunoblotting, respectively. The results revealed that plasma levels of SFRP5 were positively correlated with age in the elderly Chinese cohort. Similarly, aorta SFRP5 expression was significantly higher in 15‑month‑old rats compared with 6‑month‑old rats. In vitro, SFRP5 significantly inhibited rat aortic SMC proliferation and migration that were induced by platelet‑derived growth factor (PDGF)‑BB, as well as inhibiting ROS generation. Compared with the effect of PDGF‑BB on SMCs, SFRP5 at 100 and 200 ng/ml significantly decreased SMC proliferation by 31.5 and 34.8%, respectively (P

Microglial activation has been recognized as being vital in the pathogenesis of several neurodegenerative disorders. Therefore, the identification of therapeutic drugs to prevent microglial activation and thus protect against inflam - mation-mediated neuronal injury, is required. In the present study, dextromethorphan (DM), a compound widely used in antitussive remedies that has been demonstrated to possess neuroprotective effects, was shown to reduce proinflammatory mediator production in lipopolysaccharide (LPS)-stimulated BV2 mouse microglial cells. Western blot analysis revealed that DM markedly suppressed the activation of nuclear factor-κB (NFκB), caspase-3 signaling and the expression of another inflammation‑inducing factor, heat shock protein 60 (HSP60) and heat shock factor‑1, induced by LPS in BV2 cells. Results from ELISA assay demonstrated that DM reduced the release of HSP60, nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL‑6 induced by LPS in BV2 microglia. These results were confirmed by immunofluorescence, suggesting that DM may exert a neuroprotective and anti‑inflammatory effect by inhibiting microglial activation through the HSP60‑NFκB signaling pathway. Therefore, DM may offer substantial therapeutic benefits in the treatment of neurodegenerative diseases that are accompanied by microglial activation. * Contributed equally

It has been previously identified that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are expressed in pancreatic β cells and regulate exocytosis and insulin release. It is known that protein interacting with C‑kinase 1 (PICK1) regulates trafficking and synaptic targeting of AMPARs in the central nervous system. However, it is unknown whether PICK1 regulates glutamate‑induced insulin release in β cells. The present study demonstrated that glutamate‑induced exocytosis was increased in β cells derived from PICK1‑knockout mice. In agreement with this result, adding PICK1 in β cells reduced glutamate‑induced exocytosis, whereas adding EVKI, a peptide that interrupts the interaction between AMPARs and PICK1, increased the exocytosis of β cells with the application of glutamate. Furthermore, the conductance of ATP‑sensitive potassium (KATP) channels was reduced in PICK1‑knockout mice, which was reversed by the overexpression of PICK1. In addition, PICK1 application reduced voltage oscillation induced by the closure of KATP. Taken together, the results indicate that PICK1 regulates glutamate‑induced exocytosis in β cells.