Arctiin is a lignin isolated from Arctium lappa which has been known to have anti-viral and anti-inflammatory effects. The aim of this study is to explore the protective effect of arctiin on lipopolysaccharide (LPS)-induced inflammatory responses in acute lung injury (ALI) model of mice. Male BALB/c mice were pretreated with commercial arctiin (10, 20, and 40 mg/kg) 1 h prior to LPS challenge. Twelve hours later, airway inflammation was assessed. We assessed the effects of arctiin on the LPS-induced production of TNF-α, IL-6, and IL-1β in the bronchoalveolar lavage fluid (BALF). The lung wet-to-dry weight ratio, myeloperoxidase (MPO) activity, and inflammatory signaling pathway were also detected. Our results showed that arctiin not only significantly ameliorated LPS-stimulated lung histopathological changes but also reduced the lung MPO activity. Arctiin also dramatically decreased the production of TNF-α, IL-1β, and IL-6 in the BALF. In addition, arctiin significantly inhibited LPS-induced PI3K/Akt phosphorylation as well as NF-κB activation. In conclusion, our results suggested that arctiin protected against LPS-induced ALI through inhibiting PI3K/AKT/NF-κB signaling pathway.

BackgroundAchilles tendons are the most common sites of tendon xanthomas that are commonly caused by disturbance of lipid metabolism. Achilles tendon thickening is the early characteristic of Achilles tendon xanthomas. The relationship between Achilles tendon thickness (ATT) and LDL-C levels, and risk factors of ATT in patients with hypercholesterolemia, have thus far been poorly documented.MethodsA total of 205 individuals, aged 18-75 years, were enrolled from March 2014 to March 2015. According to the LDL-C levels and the “Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults”, all subjects were divided into 3 groups: normal group (LDL-C < 3.37 mmol/L, n = 51); borderline LDL-C group (3.37 mmol/L ≤ LDL-C ≤ 4.12 mmol/L, n = 50); and hypercholesterolemia group (LDL ≥ 4.14 mmol/L, n = 104). ATT was measured using a standardized digital radiography method and the results were compared among the 3 groups. The correlation between ATT and serum LDL-C levels was analyzed by Pearson’s correlation, and the risk factors of ATT were determined by the logistic regression model.ResultsATT in borderline LDL-C group was 8.24 ± 1.73 mm, markedly higher than 6.05 ± 0.28 mm of normal group (P < 0.05). ATT in hypercholesterolemia group was 9.42 ± 3.63 mm which was significantly higher than that of normal group (P < 0.005) and that of borderline LDL-C group (P < 0.05). There was a positive correlation between the serum LDL-C levels and ATT (r = 0.346, P < 0.001). The serum LDL-C level was a risk factor (OR = 1.871, 95% CI: 1.067-3.280) while the levels of HDL-C (OR = 0.099, 95% CI: 0.017-0.573) and Apo AI (OR = 0.035, 95% CI: 0.003-0.412) were protective factors of ATT.ConclusionsATT might serve as a valuable auxiliary diagnostic index for hypercholesterolemia and used for the assessment and management of cardiovascular disease.

Mitochondrial dysfunction has been associated with the pathogenesis of a variety of neurodegenerative diseases. Sitagliptin is a dipeptidyl‐peptidase‐4 (DPP‐4) inhibitor that has been approved for the treatment of type 2 diabetes (T2DM). In the current study, we report that sitagliptin increased the expression of PGC‐1α, NRF1, and TFAM in human SH‐SY5Y neuronal cells. Notably, our data indicate that sitagliptin promoted mitochondrial biogenesis by increasing the amount of mtDNA, the levels of mitochondria‐related genes such as TOMM20, TOMM40, TIMM9, NDUFS3, ATP5C1, and the expression of oxidative phosphorylation subunits complex I and complex IV. Additionally, we found that sitagliptin induced a “gain of mitochondrial function” in SH‐SY5Y cells by increasing the mitochondrial respiratory rate and adenosine triphosphate (ATP) production. Significantly, our results demonstrate that sitagliptin activated the transcriptional factor CREB by inducing its phosphorylation at Ser133. Inhibition of CREB using its specific inhibitor H89 abolished the effects of sitagliptin on the expression of PGC‐1α, NRF1, and TFAM, as well as an increase in mtDNA amount and ATP production. These findings suggest that sitagliptin could become a potential agent for the treatment of neurological disorders.

Summary. -Swine influenza virus (SIV), one of the most important zoonotic agents, is associated with major public health concerns. The current study was conducted to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in the regulation of the inflammatory response to acute lung injury (ALI) induced by SIV of H9N2 subtype (H9N2-SIV) in mice. For this purpose, BALB/c mice were intranasally infected with 20 LD 50 of H9N2-SIV (infected group), while non-infected mice served as control (control group). To assess the effect of p38 MAPK, its specific inhibitor SB203580 was employed followed by SIV infection (SB group). At various times after infection, mouse lungs were subjected to pathological and histological observations and detection of inflammatory cytokines tumor necrosis factor α (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 and phosphorylated p38 MAPK. The obtained results showed obvious inflammatory responses, injury and raised levels of inflammatory cytokines and phosphorylated p38 MAPK in the lungs of virus-infected mice. In the mice inoculated with the virus alone, the level of phosphorylated p38 MAPK increased from day 2 and peaked at day 6 post infection (p.i.). However, SB203580 caused lower increases in inflammatory cytokines and phosphorylated p38 MAPK and a milder lung injury. These findings indicate that the activation of p38 MAPK upregulated the inflammatory responses to H9N2-SIV-induced ALI, increased its severity and promoted the production of inflammatory cytokines.Keywords: p38 MAPK; swine influenza virus; inflammatory response; acute lung injury; SB203580; mouse * Corresponding author. E-mail: hbzjkwd@163.com; xutong1969@ sohu.com; phone: +86-18931318516. Abbreviations: ALI = acute lung injury; IL = interleukin; MAPK = mitogen-activated protein kinase; p.i. = post infection; i.p. = intraperitoneally; SB group = SB203580; SIV = swine influenza virus; TNF-α = tumor necrosis factor α; W/D = wet/dry weight ratios

Myocardial infarction is a leading cause of mortality worldwide, and timely blood/oxygen reperfusion may substantially improve the outcome of infarction. However, ischemia/reperfusion (I/R) may cause severe side effects through excess reactive oxygen species generation. To develop novel methods to relieve I/R induced cell damage, the present study used a component of traditional Chinese medicine. In the present study, isolated heart tissue from aged mice and H9C2 cells with chemically-induced aging were used as experimental subjects, and it was demonstrated that formononetin was able to alleviate I/R-induced cell or tissue apoptosis. By applying formononetin to I/R-damaged tissue or cells, it was demonstrated that formononetin was able to enhance autophagy and thus alleviate I/R-induced cell damage. Furthermore, it was observed that I/R was able to inhibit lysosomal degradation processes in aged tissues or cells by impairing the lysosome acidification level, and formononetin was able to reverse this process via the re-acidification of lysosomes. In conclusion, the present study demonstrated that formononetin was able to alleviate I/R-induced cellular apoptosis in aged cells by facilitating autophagy.

Purpose Many researches have investigated the functions of tetramethylpyrazine (TMP) in Alzheimer's disease (AD). This study aimed to discuss the underlying mechanism of TMP in AD mice. Methods TMP (200 mg/kg) was administered to 6-month-old APP/PS1 transgenic mice, and behavioral changes and hippocampal nerve injury in AD mice were detected. Apoptosis and autophagy-related protein levels were detected. Changes in gene expression before and after TMP treatment were compared using transcriptome sequencing. The effects of Cullin 4B (CUL4B) overexpression and somatostatin receptor 4 (SSTR4) silencing on AD symptoms and SSTR4 ubiquitination in APP/PS1 mice were observed. SH-SY5Y and PC12 cells were treated with 25 μmol/L Aβ 25–35 and TMP to observe cell viability, apoptosis, and autophagy. Cell viability and apoptosis were measured again after treatment with proteasome inhibitor MG132 or lysosomal inhibitor 3-mA. Results TMP treatment improved the behavioral cognition of APP/PS1 mice and improved the neuronal apoptosis and damage in brain tissue. CUL4B was significantly upregulated in APP/PS1 mouse brain tissue, and SSRT4 protein was downregulated, and the levels of CUL4B and SSRT4 were negatively correlated. TMP treatment downregulated CUL4B, inhibited SSRT4 ubiquitination and upregulated SSRT4 protein level in APP/PS1 mouse brain tissue, while CUL4B overexpression or SSRT4 silencing reversed the effect of TMP. TMP and MG132 improved the decreased activity, increased apoptosis and increased SSRT4 protein in SH-SY5Y and PC12 cells treated with Aβ 25–35 , but not 3-mA. CUL4B overexpression promoted the ubiquitination of SSTR4 in cells, which partially reversed the effect of TMP. Conclusion TMP could improve the cognitive ability of AD mice by inhibiting CUL4B expression and the ubiquitination degradation of SSTR, and alleviating neuronal apoptosis and injury. This study may offer a new therapeutic option for AD treatment.