Strategies for Oral Delivery of Metal-Saturated Lactoferrin

2019 ◽  
Vol 20 (11) ◽  
pp. 1046-1051 ◽  
Author(s):  
Przemysław Gajda-Morszewski ◽  
Klaudyna Śpiewak-Wojtyła ◽  
Maria Oszajca ◽  
Małgorzata Brindell

Lactoferrin was isolated and purified for the first time over 50-years ago. Since then, extensive studies on the structure and function of this protein have been performed and the research is still being continued. In this mini-review we focus on presenting recent scientific efforts towards the elucidation of the role and therapeutic potential of lactoferrin saturated with iron(III) or manganese(III) ions. The difference in biological activity of metal-saturated lactoferrin vs. the unmetalated one is emphasized. The strategies for oral delivery of lactoferrin, are also reviewed, with particular attention to the metalated protein.

2008 ◽  
Vol 74 (24) ◽  
pp. 7821-7823 ◽  
Author(s):  
Kai Linke ◽  
Nagarajan Periasamy ◽  
Matthias Ehrmann ◽  
Roland Winter ◽  
Rudi F. Vogel

ABSTRACT High hydrostatic pressure (HHP) is suggested to influence the structure and function of membranes and/or integrated proteins. We demonstrate for the first time HHP-induced dimer dissociation of membrane proteins in vivo with Vibrio cholerae ToxR variants in Escherichia coli reporter strains carrying ctx::lacZ fusions. Dimerization ceased at 20 to 50 MPa depending on the nature of the transmembrane segments rather than on changes in the ToxR lipid bilayer environment.


2021 ◽  
Vol 22 (23) ◽  
pp. 12921
Author(s):  
Irina Giralt ◽  
Gabriel Gallo-Oller ◽  
Natalia Navarro ◽  
Patricia Zarzosa ◽  
Guillem Pons ◽  
...  

The Wnt/β-catenin signaling pathway plays a pivotal role during embryogenesis and its deregulation is a key mechanism in the origin and progression of several tumors. Wnt antagonists have been described as key modulators of Wnt/β-catenin signaling in cancer, with Dickkopf-1 (DKK-1) being the most studied member of the DKK family. Although the therapeutic potential of DKK-1 inhibition has been evaluated in several diseases and malignancies, little is known in pediatric tumors. Only a few works have studied the genetic inhibition and function of DKK-1 in rhabdomyosarcoma. Here, for the first time, we report the analysis of the therapeutic potential of DKK-1 pharmaceutical inhibition in rhabdomyosarcoma, the most common soft tissue sarcoma in children. We performed DKK-1 inhibition via shRNA technology and via the chemical inhibitor WAY-2626211. Its inhibition led to β-catenin activation and the modulation of focal adhesion kinase (FAK), with positive effects on in vitro expression of myogenic markers and a reduction in proliferation and invasion. In addition, WAY-262611 was able to impair survival of tumor cells in vivo. Therefore, DKK-1 could constitute a molecular target, which could lead to novel therapeutic strategies in RMS, especially in those patients with high DKK-1 expression.


2006 ◽  
Vol 2 (3) ◽  
pp. 439-442 ◽  
Author(s):  
Gregory P Dietl ◽  
Jonathan R Hendricks

Biological asymmetries are important elements of the structure and function of many living organisms. Using the Plio–Pleistocene fossil record of crab predation on morphologically similar pairs of right- and left-handed snail species, we show here for the first time, contrary to traditional wisdom, that rare left-handed coiling promotes survival from attacks by right-handed crabs. This frequency-dependent result influences the balance of selection processes that maintain left-handedness at the species level and parallels some social interactions in human cultures, such as sports that involve dual contests between opponents of opposite handedness.


Botany ◽  
2014 ◽  
Vol 92 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Valdnéa Casagrande Dalvi ◽  
Lucas Siqueira Cardinelli ◽  
Renata Maria Strozi Alves Meira ◽  
Aristéa Alves Azevedo

Colleters are secretory structures located in reproductive and (or) vegetative organs of many eudicots. In Gentianaceae Juss., the presence of foliar colleters has been neglected, and anatomical and histochemical studies are scarce. The objectives of this study were to investigate the anatomy, ontogeny, and chemical nature of the secretion found in Macrocarpaea obtusifolia (Griseb.) Gilg colleters to establish a relationship between their structure and function and check whether these structures are similar to those described for other genera of the Gentianaceae and other families of the Gentianales. Samples of leaves at different developmental stages were collected and processed for anatomical and histochemical analysis using light microscopy and scanning electron microscopy. Colleters in M. obtusifolia have a protodermal origin, are of standard type, and are not vascularized. Young colleters are translucent and produce an abundant amount of sticky secretion. Later, they turn yellowish with a blackened region at the apex of the head, and the secretion, composed of polysaccharides and proteins, becomes less abundant and brownish. During senescence, the process begins with complete degradation and cell collapse of the secretory portion. The colleters of the standard type in M. obtusifolia have been observed for the first time in the Gentianaceae and represent additional evidence that reinforces how common this type of colleter is in the Gentianales. Such results provide new information on the anatomy, ontogeny, histochemistry, and colleter types of Gentianaceae.


2015 ◽  
Vol 308 (4) ◽  
pp. H259-H268 ◽  
Author(s):  
Yasuhiro Maejima ◽  
Yun Chen ◽  
Mitsuaki Isobe ◽  
Åsa B. Gustafsson ◽  
Richard N. Kitsis ◽  
...  

Dysregulation of autophagy, an evolutionarily conserved process for degradation of long-lived proteins and organelles, has been implicated in the pathogenesis of human disease. Recent research has uncovered pathways that control autophagy in the heart and molecular mechanisms by which alterations in this process affect cardiac structure and function. Although initially thought to be a nonselective degradation process, autophagy, as it has become increasingly clear, can exhibit specificity in the degradation of molecules and organelles, such as mitochondria. Furthermore, it has been shown that autophagy is involved in a wide variety of previously unrecognized cellular functions, such as cell death and metabolism. A growing body of evidence suggests that deviation from appropriate levels of autophagy causes cellular dysfunction and death, which in turn leads to heart disease. Here, we review recent advances in understanding the role of autophagy in heart disease, highlight unsolved issues, and discuss the therapeutic potential of modulating autophagy in heart disease.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 857 ◽  
Author(s):  
Cora Roehlecke ◽  
Mirko H. H. Schmidt

Intercellular communication among cancer cells and their microenvironment is crucial to disease progression. The mechanisms by which communication occurs between distant cells in a tumor matrix remain poorly understood. In the last two decades, experimental evidence from different groups proved the existence of thin membranous tubes that interconnect cells, named tunneling nanotubes, tumor microtubes, cytonemes or membrane bridges. These highly dynamic membrane protrusions are conduits for direct cell-to-cell communication, particularly for intercellular signaling and transport of cellular cargo over long distances. Tunneling nanotubes and tumor microtubes may play an important role in the pathogenesis of cancer. They may contribute to the resistance of tumor cells against treatments such as surgery, radio- and chemotherapy. In this review, we present the current knowledge about the structure and function of tunneling nanotubes and tumor microtubes in cancer and discuss the therapeutic potential of membrane tubes in cancer treatment.


1897 ◽  
Vol s2-40 (157) ◽  
pp. 165-184
Author(s):  
ARTHUR WILLEY

1. This is the first time that an Enteropneust with a free pharynx has been studied in the living condition. 2. The Ptychodera flava of Eschscholtz (char. emend. mihi) is rightly assigned by Spengel to his amended genus Ptychodera, as shown by the presence of the genital pleura, of external liver saccules, and by the length of the collar region. 3. P. flava belongs to Spengel's sub-genus Chlamydothorax, as shown by the ventral origin of the genital pleura, the diffuse gonads, and the free pharynx. 4. In the fact of the gill-slits being open directly to the exterior throughout their entire length, P. flava is more closely related to P. bahamensis than to any other described species. This is also indicated by the simple rows of paired liver saccules as opposed to the irregular multiple arrangement met with in P. erythræa. 5. The genus Ptychodera. (referring more especially to the sub-genus Chlamydothorax) probably represents an archaic type, as shown by the diffuse arrangement of the gonads, the free pharynx, and its littoral habitat; and it is probably not, as Spengel supposes it to be, phylogenetically younger than the other genera of Enteropneusta. 6. The gill-slits, branchial skeleton, and the temporary atrium formed by the apposition of the genital pleura in Ptychodera, offer a general homology to the corresponding structures in Amphioxus and the Ascidians, while presenting many differences in the details of their structure and relations. 7. Some of these differences are comparatively unimportant, and such as might well be expected to occur in distantly related forms with such totally different habits of existence, while others are to be accounted for by a wide interpretation of the principle of correlation between structure and function. 8. Many differences of detailed structure in the pharyngeal wall and its skeletal supports between the Enteropneusta and Amphioxus are to be correlated with the fact that, in the former, the tongue-bars are larger (often, as in P. flava, very much larger) than the primary bars, while in the latter the reverse condition obtains.


2019 ◽  
Vol 80 (5) ◽  
pp. 281-289 ◽  
Author(s):  
Aimee L. Hanson ◽  
Craig J. Morton ◽  
Michael W. Parker ◽  
Darrell Bessette ◽  
Tony J. Kenna

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lu Yu ◽  
Siying Liu ◽  
Chen Wang ◽  
Chuanyu Zhang ◽  
Yajie Wen ◽  
...  

Abstract Background Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear. Methods In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro. Results We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells. Conclusions ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.


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