scholarly journals Tβ4–Ac-SDKP pathway: Any relevance for the cardiovascular system?

2019 ◽  
Vol 97 (7) ◽  
pp. 589-599
Author(s):  
Kamal M. Kassem ◽  
Sonal Vaid ◽  
Hongmei Peng ◽  
Sarah Sarkar ◽  
Nour-Eddine Rhaleb

The last 20 years witnessed the emergence of the thymosin β4 (Tβ4)–N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) pathway as a new source of future therapeutic tools to treat cardiovascular and renal diseases. In this review article, we attempted to shed light on the numerous experimental findings pertaining to the many promising cardiovascular therapeutic avenues for Tβ4 and (or) its N-terminal derivative, Ac-SDKP. Specifically, Ac-SDKP is endogenously produced from the 43-amino acid Tβ4 by 2 successive enzymes, meprin α and prolyl oligopeptidase. We also discussed the possible mechanisms involved in the Tβ4–Ac-SDKP-associated cardiovascular biological effects. In infarcted myocardium, Tβ4 and Ac-SDKP facilitate cardiac repair after infarction by promoting endothelial cell migration and myocyte survival. Additionally, Tβ4 and Ac-SDKP have antifibrotic and anti-inflammatory properties in the arteries, heart, lungs, and kidneys, and stimulate both in vitro and in vivo angiogenesis. The effects of Tβ4 can be mediated directly through a putative receptor (Ku80) or via its enzymatically released N-terminal derivative Ac-SDKP. Despite the localization and characterization of Ac-SDKP binding sites in myocardium, more studies are needed to fully identify and clone Ac-SDKP receptors. It remains promising that Ac-SDKP or its degradation-resistant analogs could serve as new therapeutic tools to treat cardiac, vascular, and renal injury and dysfunction to be used alone or in combination with the already established pharmacotherapy for cardiovascular diseases.

2010 ◽  
Vol 46 (4) ◽  
pp. 607-616 ◽  
Author(s):  
Daiane Hansen ◽  
Mitsue Haraguchi ◽  
Antonio Alonso

The plant of the genus Pterodon (Fabaceae, Leguminosae), commonly known as 'sucupira' or 'faveira', are disseminated throughout the central region of Brazil and has frequently been used in popular medicine for its anti-rheumatic, analgesic, and anti-inflammatory properties. In recent years, interest in these plants has increased considerably. The biological effects of different phytoextracts and pure metabolites have been investigated in several experimental models in vivo and in vitro. The literature describes flavonoids, triterpene and steroids, while one paper presented studies with proteins isolated from the genus. This review provides an overview of phytochemical and pharmacological research in Pterodon, showing the main chemical compounds studied to date, and focusing on the relationship between these molecules and their biological activity. Furthermore, this study paves the way for more in-depth investigation, isolation and characterization of the molecules of this plant genus.


Author(s):  
Griet Glorieux ◽  
Nathalie Neirynck ◽  
Anneleen Pletinck ◽  
Eva Schepers ◽  
Raymond Vanholder

The uraemic syndrome is a complex mixture of organ dysfunctions attributed to the retention of a multitude of compounds that under normal conditions are excreted by healthy kidneys. Although important progress has been made in the identification and characterization of uraemic retention solutes and in the revealing of their pathophysiological effects, this knowledge remains far from complete. Data are discussed on general characteristics of specific uraemic retention solutes, on in vitro and in vivo biological effects and on available observational and interventional studies with respect to their removal and related patient outcome are discussed.


Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 94 ◽  
Author(s):  
Denise Murgia ◽  
Rodolfo Mauceri ◽  
Giuseppina Campisi ◽  
Viviana De Caro

The natural polyphenol Resveratrol (RSV) claims numerous positive effects on health due to the well documented biological effects demonstrating its potential as a disease-preventing agent and as adjuvant for treatment of a wide variety of chronic diseases. Since several studies, both in vitro and in vivo, have highlighted the protective bone aptitude of RSV both as promoter of osteoblasts’ proliferation and antagonist of osteoclasts’ differentiation, they could be interesting in view of applications in the field of dentistry and maxillofacial surgery. This review has brought together experimental findings on the use of RSV in the regeneration of bone tissue comprising also its application associated with scaffolds and non-transfusional hemocomponents.


Author(s):  
Н.В. Белобородова ◽  
В.В. Мороз ◽  
А.Ю. Бедова

Интеграция метаболизма макроорганизма и его микробиоты, обеспечивающая в норме симбиоз и саногенез, нарушается при заболеваниях, травме, критическом состоянии, и вектор взаимодействия может изменяться в пользу прокариотов по принципу «метаболиты бактерий - против хозяина». Анализ литературы показал, что, с одной стороны, имеется живой интерес к ароматическим микробным метаболитам, с другой - отсутствует четкое представление об их роли в организме человека. Публикации, касающиеся ряда ароматических микробных метаболитов (фенилкарбоновых кислот, ФКК), как правило, не связаны между собой по тематике и направлены на решение тех или иных прикладных задач в разных областях биологии и медицины. Цель обзора - анализ информации о происхождении, биологических эффектах ФКК в экспериментах in vitro и in vivo , и клинических наблюдениях. Обобщая результаты приведенных в обзоре исследований на клеточном, субклеточном и молекулярном уровнях, логично предположить участие ароматических микробных метаболитов в патогенезе полиорганной недостаточности при сепсисе. Наиболее перспективным для раскрытия роли ароматических микробных метаболитов представляется изучение механизмов вторичной почечной недостаточности и септической энцефалопатии. Важным направлением для будущих исследований является изучение влияния продуктов микробной биодеградации ароматических соединений на развитие диссеминированного внутрисосудистого свертывания крови, артериальной гипотензии и септического шока. Результаты дальнейших исследований будут иметь не только фундаментальное значение, но и обогатят практическую медицину новыми диагностическими и лечебными технологиями. Significant increases in blood concentrations of some aromatic metabolites (phenylcarboxylic acids, PhCAs) in patients with sepsis have been previously shown. Enhanced bacterial biodegradation of aromatic compounds has been demonstrated to considerably contribute to this process. Integration of macroorganism metabolism and its microbiota, which provides normal symbiosis and sanogenesis, is disturbed in diseases, trauma, and critical conditions. Direction of this interaction may change in favor of prokaryotes according to the principle, “bacterial metabolites are against the host”. Analysis of literature showed a particular interest of many investigators to aromatic microbial metabolites. However, there is no clear understanding of their role in the human body. Publications on PhCAs are generally not thematically interrelated and usually focus on solving applied tasks in different fields of biology and medicine. The aim of this work was to consolidate existing information about origin and biological effects of PhCAs in in vitro / in vivo experiments and some clinical findings. The presented summary of reported data from studies performed at cellular, sub-cellular, and molecular levels suggests participation of aromatic microbial metabolites in the pathogenesis of multiple organ failure in sepsis. Studying mechanisms of secondary renal failure and septic encephalopathy is most promising for discovering the function of aromatic microbial metabolites. Effects of microbial biodegradation products of aromatic substances on development of disseminated intravascular coagulation, hypotension, and septic shock are an important challenge for future studies. Results of further investigations will be not only fundamental, but will also enrich medical practice with new diagnostic and therapeutic technologies.


2019 ◽  
Author(s):  
Priya Prakash ◽  
Travis Lantz ◽  
Krupal P. Jethava ◽  
Gaurav Chopra

Amyloid plaques found in the brains of Alzheimer’s disease (AD) patients primarily consists of amyloid beta 1-42 (Ab42). Commercially, Ab42 is synthetized using peptide synthesizers. We describe a robust methodology for expression of recombinant human Ab(M1-42) in Rosetta(DE3)pLysS and BL21(DE3)pLysS competent E. coli with refined and rapid analytical purification techniques. The peptide is isolated and purified from the transformed cells using an optimized set-up for reverse-phase HPLC protocol, using commonly available C18 columns, yielding high amounts of peptide (~15-20 mg per 1 L culture) in a short time. The recombinant Ab(M1-42) forms characteristic aggregates similar to synthetic Ab42 aggregates as verified by western blots and atomic force microscopy to warrant future biological use. Our rapid, refined, and robust technique to purify human Ab(M1-42) can be used to synthesize chemical probes for several downstream in vitro and in vivo assays to facilitate AD research.


2019 ◽  
Author(s):  
C. Tigrine ◽  
A. Kameli

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.


2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.


2019 ◽  
Vol 18 (14) ◽  
pp. 1983-1990 ◽  
Author(s):  
V. Lenin Maruthanila ◽  
Ramakrishnan Elancheran ◽  
Ajaikumar B. Kunnumakkar ◽  
Senthamaraikannan Kabilan ◽  
Jibon Kotoky

Emerging evidence present credible support in favour of the potential role of mahanine and girinimbine. Non-toxic herbal carbazole alkaloids occur in the edible part of Murraya koenigii, Micromelum minutum, M. zeylanicum, and M. euchrestiolia. Mahanine and girinimbine are the major potent compounds from these species. In fact, they interfered with tumour expansion and metastasis development through down-regulation of apoptotic and antiapoptotic protein, also involved in the stimulation of cell cycle arrest. Consequently, these compounds were well proven for the in-vitro and in vivo evaluation that could be developed as novel agents either alone or as an adjuvant to conventional therapeutics. Therefore, mahanine and girinimbine analogs have the potential to be the promising chemopreventive agents for the tumour recurrence and the treatment of human malignancies. In this review, an updated wide-range of pleiotropic anticancer and biological effects induction by mahanine and girinimbine against cancer cells were deeply summarized.


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