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Abstract

Use of huge amounts of antibiotics in farm animal production has promoted the prevalence of antibiotic-resistant bacteria, which poses a serious threat to public health. Therefore, alternative approaches are needed to reduce or replace antibiotic usage in the food animal industry. PR-39 is a pig-derived proline-rich antimicrobial peptide that has a broad spectrum of antibacterial activity and a low propensity for development of resistance by microorganisms. To test whether ubiquitous expression of PR-39 in transgenic (TG) mice can increase resistance against bacterial infection, we generated TG mice that ubiquitously express a pig-derived antimicrobial peptide PR-39 and analyzed their growth and resistance to infection of the highly pathogenic Actinobacillus pleuropneumoniae (APP) isolated from swine. The growth performance was significantly increased in TG mice compared with their wild-type (WT) littermates. After the APP challenge, TG mice exhibited a significantly higher survival rate and significantly lower tissue bacterial load than WT littermates. Furthermore, the tissue lesion severity that resulted from APP infection was milder in TG mice than that in their WT littermates. This study provides a good foundation for the development of PR-39-expressing TG animals, which could reduce the use of antibiotics in the farm animal industry.

Keywords

Antimicrobial peptides PR-39 Transgenic animals Actinobacillus pleuropneumoniae infection Growth

Abstract

Background

Angiopoietin-like protein 8(ANGPTL8) and apolipoprotein CIII (apoCIII) were found to inhibit the activity of lipoprotein lipase (LPL) and disrupt the clearance of triglyceride-rich lipoproteins (TRLs), leading to hypertriglyceridemia. Whether any relationship exists between these two important modulators of triglyceride metabolism has not been reported. Besides, whether ANGPTL8 concentration is altered in the patients with coronary artery disease (CAD) is still unclear.

Methods

A hospital-based case-control study was conducted. Sixty-eight CAD subjects and fifty-two nonCAD controls were recruited. Plasma apoCIII, ANGPTL8 was measured.

Results

ANGPTL8 and apoCIII concentration exhibited no significant difference between CAD group and nonCAD group. Both ANGPTL8 and apoCIII were significantly correlated with triglyceride level(r = − 0.243, P = 0.008; r = 0.335, P < 0.001, respectively). Regression analysis revealed that apoCIII was an independent contributor to triglyceride level independent of ANGPTL8 concentration (standardized beta= 0.230, P < 0.01).

Conclusion

ApoCIII may mediate the effects of ANGPTL8 on triglyceride metabolism.

Keywords

ANGPTL8 apoCIII Triglyceride Coronary artery disease

Abstract

Ischemia-reperfusion (I/R) injury is a pathological process which magnifies with the ensuing inflammatory response and endures with the increase of oxidants especially during reperfusion. The present study was conducted to assess the possible modulatory effects of plumbagin, the active constituent extracted from the roots of traditional medicinal plant Plumbago zeylanica L., on the dire role of high mobility group box 1 (HMGB1) as well as the associated inflammation, oxidative stress and apoptotic cell death following hepatic I/R. Four groups of rats were included: sham-operated, sham-operated treated with plumbagin, I/R (30?min ischemia and 1?h reperfusion) and I/R treated with plumbagin. Pretreatment with plumbagin markedly improved hepatic function and structural integrity compared to the I/R group, as manifested by depressed plasma transaminases and lactate dehydrogenase (LDH) activities as well as alleviated tissue pathological lesions. Plumbagin prominently hampered HMGB1 expression and subsequently quelled inflammatory cascades, as nuclear factor kB (NF-kB), tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO) activity. It also interrupted reactive oxygen species (ROS)-HMGB1loop as evident by restored liver reduced glutathione (GSH), elevated glutathione peroxidase (GPx) activity, along with decreased liver lipid peroxidation. Simultaneously, plumbagin significantly ameliorated apoptosis by amending the mRNA expressions of both anti-apoptotic (Bcl-2) and pro-apoptotic (Bax). The present results revealed that plumbagin is endowed with hepatoprotective activity ascribed to its antioxidant, anti-inflammatory and anti-apoptotic properties which are partially mediated through dampening of HMGB1 expression.

The association between norepinephrine and metabolism in patients with major depression

Posted by J Futtrup, M Nordentoft, B Elfving, et al. on 2018-07-19 18:51:09

Abstract

Background

Previous studies indicate that levels of plasma norepinephrine (p-NE) are altered in depressed patients. However, it is unclear whether altered NE metabolism is involved in the pathogenic association between depression and cardiovascular disease. The aim of the present study was, firstly, to investigate if p-NE levels differ between patients with major depression and healthy controls. Secondly, the study sought to assess the associations between p-NE and metabolic variables in all participants. The third and final aim of the study was to assess if the associations between p-NE and metabolic variables are influenced by disease status (depression vs. healthy).

Methods

108 patients with major depression and 44 healthy controls were tested for levels of p-NE and metabolic variables that affect cardiovascular risk.

Results

The median level of p-NE in depressed patients (DSM-IV) was 2636 pg/ml, (IQR 2094–3143) and 2279 pg/ml (IQR 2007–2562) in non-depressed controls (p = 0.013). However, the difference between p-NE levels was non-significant when adjusted for daily smoking (p = 0.138). Significant associations (p ≤ 0.05) were observed between p-NE and p-lipids, mean arterial blood pressure, p-insulin, quantitative insulin sensitivity check index as well as inflammatory markers.

Conclusions

Elevated levels of p-NE observed in patients with major depression were attributable to daily smoking, rather than to the depressive disorder. Important associations were found between p-NE and metabolic variables that affect cardiovascular risk. This is interesting from a clinical point of view, since affected individuals may benefit from simple and inexpensive treatments that influence sympathetic activity. All associations were independent of disease status.

Abstract

Background aims

TNFR family member glucocorticoid-induced tumor necrosis factor–related receptor (GITR/TNFRSF18) activation by its ligand glucocorticoid-induced TNF-related receptor ligand (GITRL) have important roles in proliferation, death and differentiation of cells. Some types of small cell lung cancers (SCLCs) express GITR. Because mesenchymal stromal cells (MSCs) may target tumor cells, we aimed to investigate the effect of MSCs carrying GITRL overexpressing plasmid on the proliferation and viability of a GITR+ SCLC cell line (SCLC-21H) compared with a GITR– SCLC cell line (NCI-H82).

Methods

Electroporation was used to transfer pGITRL (GITRL gene carrying plasmid) or pCR3 (mock plasmid) into MSCs. Flow cytometry and semi-quantitative polymerase chain reaction were used to characterize the transfected MSCs. Following SCLC-21H or NCI-H82 cell lines were co-cultured with pGITRL-MSCs.

Results

Proliferation of NCI-H82 was increased in all types of co-cultures while SCLC-21H cells did not. GITRL expressing MSCs were able to induce cell death of SCLC-21H through the upregulation of SIVA1 apoptosis inducing factor.

Conclusions

The influence of MSCs on SCLC cells can vary according to the cancer cell subtypes as obtained in SCLC-21H and NCI-H82 and enabling GITR-GITRL interaction can induce cell death of SCLC cell lines.

Key Words

apoptosis; cell-based gene delivery; genetically modified MSCs; GITRL; mesenchymal stromal cell; small cell lung cancer; SIVA

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