Current Pharmaceutical Biotechnology - Volume 19, Issue 10, 2018

The invasion of an extravillous trophoblast (EVT) into maternal decidual tissues, especially towards maternal spiral arteries, is an essential process in the human placental formation and subsequent normal fetal development. However, the precise regulatory mechanisms to induce EVT invasion towards arteries and/or to protect EVT from further invasion are not well understood. We found that a chemokine receptor, CCR1, was specifically expressed on EVT migrating towards maternal arteries. Using EVT isolated from a primary villous explant culture, RANTES, which is one of the ligands for CCR1, was shown to enhance EVT invasion. Furthermore, we observed that the platelets were deposited among intravascular EVT and platelet-derived soluble factors, which contained RANTES, enhanced EVT invasion. On the one hand, dipeptidyl peptidase IV (DPPIV), which can metabolize RANTES on the cell surface, was expressed on non-invading EVT and was demonstrated to suppress EVT invasion. In contrast, laeverin/aminopeptidase Q, which is specifically expressed on EVT, was shown to induce EVT invasion. Also, CD9 which is a cell surface marker of platelets and a regulator of integrin function was expressed on EVT and gene knockdown of the CD9 molecule enhanced EVT invasion. These findings suggest that the chemokine-chemokine receptor, chemokine-peptidase, and CD9-integrin systems play important roles in the regulation of EVT invasion during early human placental formation.

Background: The pregnancy pathology preeclampsia is still among the leading causes of maternal and perinatal morbidity and mortality. At the same time, its etiology is far from being identified and remains obscure in a number of facets. A number of hypotheses have been developed to explain the altered interplay between placenta and mother leading to the clinical symptoms of preeclampsia. However, none of them offers the opportunity to explain the variability of cases with late-onset versus early-onset, mild versus severe and with or without additional fetal growth restriction. Conclusion: This paper identifies the weaknesses of the most important current hypothesis and at the same time offers a set of new elucidations including maternal susceptibility, and villous/extravillous trophoblast differentiation to explain the development of preeclampsia. Such elucidations allow following new scientific routes and pathways to untangle the etiology of preeclampsia.

Preeclampsia is the leading cause of death and morbidity worldwide for the mother and fetus during pregnancy. Preeclampsia does not only affect the mother and the baby during pregnancy, but can also have long-term effects, such as the increased risk of hypertension and cardiovascular disease on the offspring and the postpartum mother later in life. The exact cause of preeclampsia is unknown, but women with preeclampsia have elevated concentrations of agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). These AT1-AA's through multiple studies have shown to play a significant role in the pathology and possible genesis of preeclampsia. This review will discuss the discovery of AT1-AAs and the role of AT1-AAs in the pathophysiology of preeclampsia. This review will also discuss future therapeutic approaches towards the AT1-AA to prevent adverse pregnancy outcomes. Furthermore, we will examine the relationship between AT1-AA induced hypertension associated with increased oxidative stress, antiangiogenic factors (such as soluble fms-related tyrosine kinase-1 (sFlt-1), endothelin-1 (ET-1), inflammation, endothelial dysfunction, and reduced renal function. Understanding the pathological role of AT1-AAs in hypertensive pregnancies is important as we search for novel therapies to manage preeclampsia.

Preeclampsia is one of the most serious pregnancy - specific medical conditions of increasing incidence. It remains a major cause of maternal and fetal morbidity and mortality. Although maternal mortality is especially high in developing countries, preeclampsia and its complications are one of the top four causes of maternal deaths even in developed societies. Unfortunately, yet the only effective and definitive treatment of preeclampsia is delivery of the baby and placenta, and its time depends on the disease severity and gestational age. In this review, we report principles of management of preeclampsia in the light of current international recommendations. Suggested failure of the placental development and significant role of angiogenic factors and their receptors in etiology of preeclampsia give the possibility for their future use in diagnosis and risk assessment of the disease and open new chapter of possible solutions also in the field of treatment of this serious pregnancy complication. Introduction of an advanced form of therapy that could safely prolong the duration of pregnancy would be invaluable in the area of preeclampsia management and lowering perinatal complications, especially in women with early-onset severe preeclampsia.

Preeclampsia is one of the most serious pregnancy - specific medical conditions affecting 3- 6% of all gestations. It remains a leading cause of maternal and fetal morbidity and mortality. The aetiology of preeclampsia is not fully elucidated yet, although a huge progress has been made in its understanding within the last decade. Numerous studies have provided compelling evidence that an excess of some antiangiogenic molecules released by the placenta to maternal circulation, in particular soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) and decreased levels of proangiogenic substances like placental growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) play a key role in the pathogenesis of preeclampsia. In this review, we report recent knowledge about possible predictive, diagnostic and therapeutic roles of these pro- and antiangiogenic biomarkers as well as analyzed the background of their use in these fields. Discoveries in the area of circulating factors of angiogenesis are exciting and give promising perspectives for future clinical management of preeclampsia. Currently, it can be difficult, especially in developing countries due to high cost of such studies.

HELLP syndrome is a disorder associated with serious maternal morbidity and mortality. Distinguishing HELLP from other pregnancy-related disorders is often challenging and may result in delay of treatment. Differential diagnoses include acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, antiphospholipid syndrome, and hemolytic uremic syndrome, and are reviewed in this chapter. While there is not any current treatment for HELLP, the mainstay of treatment involves maternal stabilization and timely delivery. Various treatment strategies have been attempted to help decrease the morbidity and mortality of HELLP, including the maternal use of corticosteroids. The authors review the studies and controversies surrounding the maternal use of corticosteroids, plasma exchange, and low molecular weight heparin for the treatment of HELLP, as well as the role of the complement system in HELLP. Further large, well-designed, randomized controlled trials are needed to address the role corticosteroids may play in the treatment of women with HELLP and to help improve maternal and fetal outcomes.

Atopic dermatitis is a chronic inflammatory skin disease that commonly occurs in early childhood. To date, the pharmacological treatment of atopic dermatitis is far from ideal, poses several limitations, and constantly requires novel approaches. The theory that appropriate colonization of gut bacteria during infancy influences the development of the immune system has prompted numerous clinical trials that have evaluated the effectiveness of probiotic supplementation for the prevention and treatment of atopic eczema in children. In addition, topical application of probiotics has been demonstrated to improve the skin's barrier function, which might contribute to reduce the severity of atopic dermatitis. In this article, we review the literature and data regarding the use of probiotics, both by oral administration and topical application, for the treatment of atopic dermatitis. We also summarize the knowledge on the potential mechanisms by which probiotics influence the gut and exert their skin effects. Probiotic supplementation seems to be an attractive strategy to prevent and treat pediatric atopic dermatitis. However, to enable the treatment to be fully effective, the period of supplementation should be considered. Moreover, in future studies, a combination of probiotic supplementation and simultaneous topical application of creams containing probiotics might also be considered.

Background: Curcuminoid genes have an important role in the biosynthesis of curcumin, a valuable bioactive compound, in Curcuma species. However, there have not been any reports of these genes in Curcuma zedoaria. Objective: The present work reports on the isolation of genes encoding enzymes in curcuminoid metabolic pathway and their expression in C. zedoaria. Method: The primers were designed from untranslation regions of DCS, CURS1, CURS2 and CURS3 genes which are involved in curcuminoid biosynthesis in C. longa to isolate the corresponding fulllength genes in C. zedoaria. RT-PCR amplification and HPLC analysis are used to estimate the expression of genes and biosynthesis of curcumin in both rhizome and callus. Results: The results showed that all four genes from C. zedoaria (named CzDCS, CzCURS1, CzCURS2 and CzCURS3) and C. longa have a high identity (approximately 99%) and lengths of genes from C. zedoaria are 1382, 1240, 1288 and 1265 nu, respectively. CzCURS1, 2 and 3 genes have one intron while CzDCS has two introns. RT-PCR amplification indicated that curcuminoid genes expressed mRNA in rhizome and callus of C. zedoaria. Curcumin, a major component of curcuminoids, was also found in callus by HPLC analysis. Conclusion: The sequence information of DCS and CURS1-3 genes in C. zedoaria will be very valuable for a subsequent study on the effects of elicitors on the transcription of genes involved in curcuminoid biosynthesis pathway.