Translational research : the journal of laboratory and clinical medicine
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Intrauterine growth restriction (IUGR) is a pathological condition of pregnancy with high perinatal mortality and morbidity, characterized by inadequate fetal growth associated to altered maternal hemodynamics with impaired uteroplacental blood flow and placental insufficiency. To date, iatrogenic premature delivery remains the elective therapeutic strategy. However, in recent years the possibility of a therapeutic approach with vasodilators and myorelaxants, such as nitric oxide (NO) donors, has gained interest. ⋯ Ex vivo experiments confirmed that NO donors increased expression and secretion of EGFL7 by villous explants. To specifically investigate the potential response of trophoblast cells to NO, we treated HTR8-sVneo cells with NO donors and observed induction of EGFL7 expression. Altogether, our findings indicate that NO induces endothelial and trophoblast expression of EGFL7 in the placenta and improves fetal growth, suggesting a correlation between placental levels of EGFL7 and pregnancy outcome.
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Aortic injuries, including aortic aneurysms and dissections, are fatal vascular diseases with distinct histopathological features in the aortic tissue such as inflammation-induced endothelial dysfunction, infiltration of immune cells, and breakdown of the extracellular matrix. Few treatments are available for treating aortic aneurysms and dissections; thus, basic and clinical studies worldwide have been attempted to inhibit disease progression. Substance P (SP) exerts anti-inflammatory effects and promotes restoration of the damaged endothelium, leading to vasculature protection and facilitation of tissue repair. ⋯ Treatment of TAI rats with SP-induced anti-inflammatory responses systemically and locally, possibly by enriching anti-inflammatory M2 monocytes in the spleen and peripheral blood at early phase of aortic injury due to β-aminopropionitrile. SP-induced immune suppression finally prevented the development of aortic dissection by limiting inflammation-mediated aortic destruction. Taken together, these results suggest that SP treatment can block aortic injury by controlling the immune-cell profile and suppressing proinflammatory responses during the initial stage of vascular disease progression.
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Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorder related to type 2 diabetes (T2D). The disease can evolve toward nonalcoholic steatohepatitis (NASH), a state of hepatic inflammation and fibrosis. There is presently no drug that effectively improves and/or prevents NAFLD/NASH/fibrosis. ⋯ Liraglutide also influenced the composition of gut microbiota induced by the MCD-diet. This included recovery of a normal Bacteroides proportion and, among the Erysipelotrichaceae family, a shift between Allobaculum and Turicibacter genera. In conclusion, liraglutide prevents accumulation of C16 and C24-ceramides/sphingomyelins species, inflammation and initiation of fibrosis in MCD-diet-fed mice liver, suggesting beneficial hepatic actions independent of weight loss and global hepatic steatosis.
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The risk of venous thromboembolism (VTE) and of recurrent VTE remain elevated in people living with HIV compared to controls still with contemporary antiretroviral therapy (ART). The pathophysiology of VTE in HIV is multi factorial and includes an interplay among traditional risk factors, HIV-specific factors, behavioral factors, exposure to ART and other therapies, coinfections, and co-morbidities.
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Charcot-Marie-Tooth (CMT) disease is the most frequent inherited neuropathy, affecting 1/1500 to 1/10000. CMT1A represents 60%-70% of all CMT and is caused by a duplication on chromosome 17p11.2 leading to an overexpression of the Peripheral Myelin Protein 22 (PMP22). ⋯ To date, CMT1A treatment is symptomatic and classic pharmacological options have been disappointing. Here, we review the past, present, and future treatment options for CMT1A, with a special emphasis on the highly promising potential of PMP22-targeted small interfering RNA and antisense oligonucleotides.