scholarly journals Key Aspects of Myo-Inositol Hexaphosphate (Phytate) and Pathological Calcifications

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4434 ◽  
Author(s):  
Felix Grases ◽  
Antonia Costa-Bauza

Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease the bioavailability of important minerals under certain circumstances. However, during the past 30 years, researchers have identified many important health benefits of phytate. Thus, 150 years have elapsed since the discovery of phytate to the first descriptions of its beneficial effects. This long delay may be due to the difficulty in determining phytate in biological media, and because phytate dephosphorylation generates many derivatives (InsPs) that also have important biological functions. This paper describes the role of InsP6 in blocking the development of pathological calcifications. Thus, in vitro studies have shown that InsP6 and its hydrolysates (InsPs), as well as pyrophosphate, bisphosphonates, and other polyphosphates, have high capacity to inhibit calcium salt crystallization. Oral or topical administration of phytate in vivo significantly decreases the development of pathological calcifications, although the details of the underlying mechanism are uncertain. Moreover, oral or topical administration of InsP6 also leads to increased urinary excretion of mixtures of different InsPs; in the absence of InsP6 administration, only InsP2 occurs at detectable levels in urine.

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1127
Author(s):  
Massimo Fresta ◽  
Antonia Mancuso ◽  
Maria Chiara Cristiano ◽  
Konrad Urbanek ◽  
Felisa Cilurzo ◽  
...  

The topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments/diseases.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhihua Sun ◽  
Peiyi Li ◽  
Xiao Wang ◽  
Shuchang Lai ◽  
Hong Qiu ◽  
...  

As the major cause of female anovulatory infertility, polycystic ovary syndrome (PCOS) affects a great proportion of women at childbearing age. Although glucagon-like peptide 1 receptor agonists (GLP-IRAs) show therapeutic effects for PCOS, its target and underlying mechanism remains elusive. In the present study, we identified that, both in vivo and in vitro, GLP-1 functioned as the regulator of proliferation and antiapoptosis of MGCs of follicle in PCOS mouse ovary. Furthermore, forkhead box protein O1 (FoxO1) plays an important role in the courses. Regarding the importance of granulosa cells (GCs) in oocyte development and function, the results from the current study could provide a more detailed illustration on the already known beneficial effects of GLP-1RAs on PCOS and support the future efforts to develop more efficient GLP-1RAs for PCOS treatment.


2018 ◽  
Author(s):  
Jung Ok Lee ◽  
Hye Jeong Lee ◽  
Yong Woo Lee ◽  
Jeong Ah Han ◽  
Min Ju Kang ◽  
...  

AbstractMeteorin-like (metrnl) is a recently identified adipomyokine that has beneficial effects on glucose metabolism. However, its underlying mechanism of action is not completely understood. In this study, we have shown that a level of metrnl increase in vitro under electrical-pulse-stimulation (EPS) and in vivo in exercise mice, suggesting that metrnl is an exercise-induced myokine. In addition, metrnl increases glucose uptake through the calcium-dependent AMPK pathway. Metrnl also increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPK-dependent manner. Phosphorylated HDAC5 interacts with 14-3-3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. The intraperitoneal injection of recombinant metrnl improves glucose tolerance in mice with high fat-induced obesity or type 2 diabetes (db/db), but this is not seen in AMPK β1β2 muscle-specific null mice (AMPK β1β2 MKO). In conclusion, we have demonstrated that metrnl induces beneficial effects on glucose metabolism via AMPK and is a promising therapeutic candidate for glucose-related diseases such as type 2 diabetes.


2019 ◽  
Vol 21 (3) ◽  
pp. 379-396
Author(s):  
S. V. Sennikov ◽  
A. A. Alshevskaya ◽  
Yu. V. Zhukova ◽  
I. A. Belomestnova ◽  
A. V. Karaulov ◽  
...  

The present review article summarizes the latest world scientific data on the role of receptors for immune mediators in regulating biological effects on the cells. For the main classes of immune regulators (interleukins, interferons, growth factors and tumor necrosis factors), the variants are presented for participation of receptors as components of cytokine/cell interaction, as proven byin vitroandin vivostudies. Ability of the receptors expression to modify characteristics and type of these interactions is shown. The data on participation of receptors for regulatory molecules in development of immune-mediated diseases of various genesis have been analyzed. It was demonstrated that the changes in the receptor expression are of great importance when evaluating functional response of the cells to the mediators and in development of pathological conditions. Current studies confirmed the data suggesting effects of receptor density upon the processes of proliferation and apoptosis, as well as metabolic processes that trigger development of autoimmune, oncological and dystrophic diseases. For all the considered classes of regulatory molecules, the change in the density of receptor expression is one of the key aspects in regulating functional activity of the cells. Thus, studying expression levels of receptors on the cell membrane is important in understanding pathogenesis, whereas changing expression level may be considered as a therapeutic target in the treatment of various diseases.


Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 244 ◽  
Author(s):  
Sebastiano Intagliata ◽  
Maria N. Modica ◽  
Ludovica M. Santagati ◽  
Lucia Montenegro

In recent years, a great deal of attention has been paid to natural compounds due to their many biological effects. Polyphenols are a class of plant derivatives that have been widely investigated for preventing and treating many oxidative stress-related pathological conditions, such as neurodegenerative and cardiovascular diseases, cancer, diabetes mellitus and inflammation. Among these polyphenols, resveratrol (RSV) has attracted considerable interest owing to its high antioxidant and free radical scavenging activities. However, the poor water solubility and rapid metabolism of RSV lead to low bioavailability, thus limiting its clinical efficacy. After discussing the main biochemical mechanisms involved in RSV biological activities, this review will focus on the strategies attempted to improve RSV effectiveness, both for systemic and for topical administration. In particular, technological approaches involving RSV incorporation into different delivery systems such as liposomes, polymeric and lipid nanoparticles, microemulsions and cyclodextrins will be illustrated, highlighting their potential clinical applications. In addition, chemical modifications of this antioxidant aimed at improving its physicochemical properties will be described along with the results of in vitro and in vivo studies.


2019 ◽  
Vol 21 (2) ◽  
pp. 209-220 ◽  
Author(s):  
S. V. Sennikov ◽  
A. A. Alshevskaya ◽  
J. V. Zhukova ◽  
I. A. Belomestnova ◽  
A. V. Karaulov ◽  
...  

The present review article summarizes the latest world scientific data on the role of receptors for immune mediators in regulating biological effects on the cells. For the main classes of immune regulators (interleukins, interferons, growth factors and tumor necrosis factors), the variants are presented for participation of receptors as components of cytokine/cell interaction, as proven by in vitro and in vivo studies. Ability of the receptors expression to modify characteristics and type of these interactions is shown. The data on participation of receptors for regulatory molecules in development of immune-mediated diseases of various genesis have been analyzed. It was demonstrated that the changes in the receptor expression are of great importance when evaluating functional response of the cells to the mediators and in development of pathological conditions. Current studies confirmed the data suggesting effects of receptor density upon the processes of proliferation and apoptosis, as well as metabolic processes that trigger development of autoimmune, oncological and dystrophic diseases. For all the considered classes of regulatory molecules, the change in the density of receptor expression is one of the key aspects in regulating functional activity of the cells. Thus, studying expression levels of receptors on the cell membrane is important in understanding pathogenesis, whereas changing expression level may be considered as a therapeutic target in the treatment of various diseases.


Author(s):  
María Angélica Rivoira ◽  
Valeria Rodriguez ◽  
Germán Talamoni ◽  
Nori Tolosa de Talamoni

Background: Naringin (NAR) is a flavonoid enriched in several medicinal plants and fruits. An increasing interest in this molecule has been emerging because it has the potential to contribute to alleviating many health problems. Objective:: This review briefly describes the NAR pharmacokinetics and it mainly focus on in vitro and in vivo animal studies showing NAR beneficial effects on cardiovascular, metabolic, neurological and pulmonary disorders and cancer. The anabolic effects of NAR on different models of bone and dental diseases are also analyzed. In addition, the evidence of the NAR action on the gastrointestinal tract is reported as well as its influence on the microbiota composition and activity. Finally, current research on NAR formulations and clinical applications are discussed. Methods: The PubMed database was searched until 2019, using the keywords NAR, naringenin, cardiovascular and metabolic disorders, neurological and pulmonary disorders, cancer, bone and dental diseases, gastrointestinal tract, microbiota, NAR formulations, clinical trials. Results: The number of studies related to the bioavailability and pharmacokinetics of NAR is limited. Positive effects of NAR have been reported on cardiovascular diseases, type 2 Diabetes mellitus (T2DM), metabolic syndrome, pulmonary disorders, neurodegenerative diseases, cancer and gastrointestinal pathologies. Current NAR formulations seem to improve its bioavailability, which would allow its clinical application. Conclusion: NAR is endowed with broad biological effects that could improve human health. Since a scarce number of clinical studies have been performed, the use of them requires more investigation in order to know better their safety, efficacy, delivery and bioavailability in humans.


Foods ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Rosalba Leuci ◽  
Leonardo Brunetti ◽  
Viviana Poliseno ◽  
Antonio Laghezza ◽  
Fulvio Loiodice ◽  
...  

Secondary metabolites from plants and fungi are stimulating growing interest in consumers and, consequently, in the food and supplement industries. The beneficial effects of these natural compounds are being thoroughly studied and there are frequent updates about the biological activities of old and new molecules isolated from plants and fungi. In this article, we present a review of the most recent literature regarding the recent discovery of secondary metabolites through isolation and structural elucidation, as well as the in vitro and/or in vivo evaluation of their biological effects. In particular, the possibility of using these bioactive molecules in the prevention and/or treatment of widely spread pathologies such as cardiovascular and neurodegenerative diseases is discussed.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2032
Author(s):  
Ying-Si Wu ◽  
Jar-Yi Ho ◽  
Cheng-Ping Yu ◽  
Chun-Jung Cho ◽  
Chia-Lun Wu ◽  
...  

Gemcitabine (GCB) resistance is a major issue in bladder cancer chemoresistance, but its underlying mechanism has not been determined. Epithelial-mesenchymal transition (EMT) has been shown to be comprehensively involved in GCB resistance in several other cancer types, but the direct connection between EMT and GCB remains unclear. This study was designed to elucidate the mechanism of EMT-related GCB resistance in bladder cancer and identify a potential phytochemical to modulate drug sensitivity. The biological effects of ellagic acid (EA) or its combined effects with GCB were compared in GCB-resistant cells and the GCB-sensitive line in terms of cell viability, apoptosis, motility, and in vivo tumorigenicity. The molecular regulation of EMT-related GCB resistance was evaluated at both the mRNA and protein expression levels. Our results indicated that TGF-β/Smad induced the overactivation of EMT in GCB-resistant cells and reduced the expression of GCB influx transporters (hCNT1 and hENT1). Moreover, ellagic acid (EA) inhibited the TGF-β signaling pathway both in vitro and in vivo by reducing Smad2, Smad3, and Smad4 expression and thereby resensitized GCB sensitivity. In conclusion, our results demonstrate that TGF-β/Smad-induced EMT contributes to GCB resistance in bladder cancer by reducing GCB influx and also elucidate the novel mechanisms of EA-mediated inhibition of TGF-β/Smad-induced EMT to overcome GCB resistance. Our study warrants further investigation of EA as an effective therapeutic adjuvant agent for overcoming GCB resistance in bladder cancer.


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.


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