scholarly journals Role of CXC chemokine receptor type 4 as a lactoferrin receptor

2017 ◽  
Vol 95 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Yoshiharu Takayama ◽  
Reiji Aoki ◽  
Ryo Uchida ◽  
Atsushi Tajima ◽  
Ayako Aoki-Yoshida
Keyword(s):  
Biological Activities ◽  
Ldl Receptor ◽  
Neutralizing Antibody ◽  
Human Keratinocytes ◽  
Akt Signaling ◽  
Target Cells ◽  
Bovine Lactoferrin ◽  
Lactoferrin Receptor ◽  
Stromal Cell Derived Factor ◽  
The Many

Lactoferrin exerts its biological activities by interacting with receptors on target cells, including LDL receptor-related protein-1 (LRP-1/CD91), intelectin-1 (omentin-1), and Toll-like receptor 4 (TLR4). However, the effects mediated by these receptors are not sufficient to fully explain the many functions of lactoferrin. C-X-C-motif cytokine receptor 4 (CXCR4) is a ubiquitously expressed G-protein coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). Lactoferrin was found to be as capable as SDF-1 in blocking infection by an HIV variant that uses CXCR4 as a co-receptor (X4-tropic HIV), suggesting that lactoferrin interacts with CXCR4. We addressed whether CXCR4 acts as a lactoferrin receptor using HaCaT human keratinocytes and Caco-2 human intestinal cells. We found that bovine lactoferrin interacted with CXCR4-containing lipoparticles, and that this interaction was not antagonized by SDF-1. In addition, activation of Akt in response to lactoferrin was abrogated by AMD3100, a small molecule inhibitor of CXCR4, or by a CXCR4-neutralizing antibody, suggesting that CXCR4 functions as a lactoferrin receptor able to mediate activation of the PI3K–Akt signaling pathway. Lactoferrin stimulation mimicked many aspects of SDF-1-induced CXCR4 activity, including receptor dimerization, tyrosine phosphorylation, and ubiquitination. Cycloheximide chase assays indicated that turnover of CXCR4 was accelerated in response to lactoferrin. These results indicate that CXCR4 is a potent lactoferrin receptor that mediates lactoferrin-induced activation of Akt signaling.

scholarly journals Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Virginia Egea ◽  
Kai Kessenbrock ◽  
Devon Lawson ◽  
Alexander Bartelt ◽  
Christian Weber ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Human Mesenchymal Stem Cells ◽  
Target Cells ◽  
Autophagic Flux ◽  
Stromal Cell Derived Factor

AbstractBone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.

scholarly journals Antioxidant and Pro-Oxidant Capacities as Mechanisms of Photoprotection of Olive Polyphenols on UVA-Damaged Human Keratinocytes

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2153
Author(s):  
Raffaella Marina Lecci ◽  
Isabella D’Antuono ◽  
Angela Cardinali ◽  
Antonella Garbetta ◽  
Vito Linsalata ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Biological Activities ◽  
Human Keratinocytes ◽  
Ldl Oxidation ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Epidermal Keratinocytes ◽  
Olive Cultivar ◽  
Human Epidermal Keratinocytes ◽  
Apoptotic Effect

A wide variety of polyphenols are reported to have considerable antioxidant and skin photoprotective effects, although the mechanisms of action are not fully known. Environmentally friendly and inexpensive sources of natural bioactive compounds, such as olive mill wastewater (OMWW), the by-product of olive-oil processing, can be considered an economic source of bioactive polyphenols, with a range of biological activities, useful as chemotherapeutic or cosmeceutical agents. Green strategies, such as the process based on membrane technologies, allow to recover active polyphenols from this complex matrix. This study aims to evaluate the antioxidant, pro-oxidant, and photoprotective effects, including the underlying action mechanism(s), of the ultra-filtered (UF) OMWW fractions, in order to substantiate their use as natural cosmeceutical ingredient. Six chemically characterized UF-OMWW fractions, from Italian and Greek olive cultivar processing, were investigated for their antioxidant activities, measured by Trolox Equivalent Antioxidant Capacity (TEAC), LDL oxidation inhibition, and ROS-quenching ability in UVA-irradiated HEKa (Human Epidermal Keratinocytes adult) cultures. The photoprotective properties of UF-OMWW were assayed as a pro-oxidant-mediated pro-apoptotic effect on the UVA-damaged HEKa cells, which can be potentially involved in the carcinogenesis process. All the UF-OMWW fractions exerted an effective antioxidant activity in vitro and in cells when administered together with UV-radiation on HEKa. A pro-oxidative and pro-apoptotic effect on the UVA-damaged HEKa cells were observed, suggesting some protective actions of polyphenol fraction on keratinocyte cell cultures.

scholarly journals A new noise detected in the ocean

2007 ◽  
Vol 87 (5) ◽  
pp. 1255-1256 ◽  
Author(s):  
Angel Guerra ◽  
Xavier Martinell ◽  
Angel F. González ◽  
Michael Vecchione ◽  
Joaquin Gracia ◽  
...  
Keyword(s):  
Ambient Noise ◽  
Sound Production ◽  
Biological Activities ◽  
Physical Processes ◽  
Defensive Strategy ◽  
Reflection And Refraction ◽  
Turbulent Pressure ◽  
In The Wild ◽  
The Many ◽  
Many Sources

Many observers have noted that the sea is full of loud sounds, both ongoing and episodic. Among the many sources of natural ambient noise are wave action, physical processes such as undersea earthquakes, and biological activities of shrimps, fish, dolphins and whales. Despite interest by acoustics experts, sound production by cephalopods has been reported only twice, both involving squid. The ‘faint poppings’ produced were thought to result from fluttering of the thin external lips of the squid's funnel while water is being expelled through it. Otherwise, no information is available on cephalopod sounds. Here we present a noise produced by a stressed common octopus. The event was filmed and recorded in the wild. The hypothesis we offer to explain how this sound was produced is cavitation, which has been documented in several biological systems. In our case, the water expelled through the funnel may have created a jet with a velocity so high that the turbulent pressure dropped locally below the vapour pressure of the water. Seawater contains gas microbubbles, which will grow in size when they are entrained in the region of low pressure. Subsequently, the bubbles collapse violently when pressure rises again. The sound produced by the octopus is like a gunshot, and distinct lights observed at the same time contradict the existence of a simple pressure wave and point to the possible presence of gas-bubbles, which would change the light intensity by reflection and refraction of the sunlight. This behaviour seems to be a defensive strategy to escape from vibration-sensitive predators.

scholarly journals Fucoxanthin induced apoptotic cell death in oral squamous carcinoma (KB) cells

2021 ◽  
Vol 17 (1) ◽  
pp. 181-191
Author(s):  
Petchi Iyappan ◽  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Biological Activities ◽  
Squamous Carcinoma ◽  
Cancer Therapeutics ◽  
Kb Cells ◽  
Oral Squamous Carcinoma ◽  
The Many

Fucoxanthin (Fx) is an active compound commonly found in the many types of seaweed with numerous biological activities. The main goal of this investigation is to explore the effect of Fx against the cell proliferation, apoptotic induction and oxidative stress in the oral squamous (KB) cell line. Cytotoxicity of Fx was determined by MTT assay. The intracellular ROS production, mitochondrial membrane potential (MMP) and apoptosis induction in KB cells were examined through DCFH-DA, Rhodamine-123 and DAPI, and dual staining techniques. Effect of Fx on the antioxidant enzymes and lipid peroxidation in the KB cells was studied through the standard procedures. Fx treated KB cells showed morphological changes and reduced cell survival, which is exhibited by the cytotoxic activity of 50 μM/ml (IC50) Fx against the KB cells. The Fx treatment considerably induced the apoptotosis cells (EB/AO) and decreased the MMP (Rh-123) in KB cells. Further, it was pointed out that there was an increased lipid peroxidation (LPO) with decreased antioxidants (CAT, SOD and GSH). These results concluded that Fx has the cytotoxic effect against KB cells and has the potential to induce the apoptosis via increased oxidative stress. Hence, the Fx can be a promising agent for the treatment of oral cancer and it may lead to the development of cancer therapeutics.

scholarly journals Triptolide Modulates the Expression of Inflammation-Associated lncRNA-PACER and lincRNA-p21 in Mycobacterium tuberculosis–Infected Monocyte-Derived Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ousman Tamgue ◽  
Julius Ebua Chia ◽  
Frank Brombacher
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Target Genes ◽  
Cell Function ◽  
Immune Cell ◽  
Biological Activities ◽  
Target Cells ◽  
Dependent Manner ◽  
Direct Targeting ◽  
Non Coding Rnas ◽  
Alamarblue Assay

Triptolide is a diterpene triepoxide, which performs its biological activities via mechanisms including induction of apoptosis, targeting of pro-inflammatory cytokines, and reshaping of the epigenetic landscape of target cells. However, the targeting of long non-coding RNAs (lncRNAs) by triptolide has not yet been investigated, despite their emerging roles as key epigenetic regulators of inflammation and immune cell function during Mycobacterium tuberculosis (Mtb) infection. Hence, we investigated whether triptolide targets inflammation-associated lncRNA-PACER and lincRNA-p21 and how this targeting associates with Mtb killing within monocyte-derived macrophages (MDMs).Using RT-qPCR, we found that triptolide induced the expression of lincRNA-p21 but inhibited the expression of lncRNA-PACER in resting MDMs in a dose- and time-dependent manner. Moreover, Mtb infection induced the expression of lincRNA-p21 and lncRNA-PACER, and exposure to triptolide before or after Mtb infection led to further increase of Mtb-induced expression of these lncRNAs in MDMs. We further found that contrary to lncRNA-PACER, triptolide time- and dose-dependently upregulated Ptgs-2, which is a proximal gene regulated by lncRNA-PACER. Also, low-concentration triptolide inhibited the expression of cytokine IL-6, a known target of lincRNA-p21. Mtb infection induced the expression of IL-6 and Ptgs-2, and triptolide treatment further increased IL-6 but decreased Ptgs-2 expression in Mtb-infected MDMs. The inverse relation between the expression of these lncRNAs and their target genes is concordant with the conception that these lncRNAs mediate, at least partially, the cytotoxic and/or anti-inflammatory activities of triptolide in both resting and activated MDMs. Using the CFU count method, we found that triptolide decreased the intracellular growth of Mtb HN878. The alamarBlue assay showed that this decreased Mtb HN878 growth was not as a result of direct targeting of Mtb HN878 by triptolide, but rather evoking MDMs’ intracellular killing mechanisms which we speculate could include triptolide-induced enhancement of MDMs’ effector killing functions mediated by lncRNA-PACER and lincRNA-p21. Altogether, these results provide proof of the modulation of lncRNA-PACER and lincRNA-p21 expression by triptolide, and a possible link between these lncRNAs, the enhancement of MDMs’ effector killing functions and the intracellular Mtb-killing activities of triptolide. These findings prompt for further investigation of the precise contribution of these lncRNAs to triptolide-induced activities in MDMs.

Nanoceuticals as an Emerging Field: Current Status and Future Prospective

2021 ◽  
Vol 17 ◽  
Author(s):  
Reetu Malik ◽  
Jyoti Rathi ◽  
Deeksha Manchanda ◽  
Manish Makhija ◽  
Deepshikha Kushwaha ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Biological Activities ◽  
Food Products ◽  
The Body ◽  
Current Status ◽  
Target Cells ◽  
Food Ingredients ◽  
Novel Foods ◽  
Quality Of Food

Background: The safety and quality of food has been a matter of great discussion throughout the centuries and the application of nanotechnology in the field of nutraceuticals i.e. nanoceuticals has improved the variety and protection of food products in many ways. Objective: Improving the quality and safety of the food products with a view to improve public health and the invasion of nanotechnological advancements in the area of nutrition has resulted in the expansion of novel foods with improved oral bioavailability as well as thermal stability. The main objective of this review is to summarize available literature on nanoceuticals including patents and clinical trials. Method: The review was extracted from the searches performed at PubMed, Google Patents and Google Scholars, etc. Data from these searches was collected and evaluated for getting the information about the available literature on the nanoceuticals. Along with this, some reported patents have also been included in this review in order to conclude the future of nanoceuticals. Result: The literature so obtained was studied thoroughly as per the requirement of the objective of this review. The details of nanoceuticals including major applications, regulatory aspects, some reported patents and clinical trials are compiled here in this review. Nanoceuticals like vitamins, antibiotics, bioactive peptides, probiotics etc., which are dispersed, absorbed or incorporated in nano diameter range sacs, having improved solubility, delivery properties, biological activities, protection against degradation and therefore having improved biological activities and delivery to the target cells and tissues in the body. Different regulations from various countries recommended that any food ingredients which results from the use of nanotechnologies must undergo safety risk assessment standards before entering into the market as nano-food. Conclusion: The idea of “nanoceuticals” is increasing enthusiasm and marketable dairy/food and food supplements. This article focuses on the history, applications, regulation aspects, patents, clinical trials and future prospects of nanoceuticals.

scholarly journals Achillea millefolium L. and Achillea biebersteinii Afan. Hydroglycolic Extracts–Bioactive Ingredients for Cosmetic Use

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3368 ◽  
Author(s):  
Katarzyna Gaweł-Bęben ◽  
Marcelina Strzępek-Gomółka ◽  
Marcin Czop ◽  
Zuriyadda Sakipova ◽  
Kazimierz Głowniak ◽  
...  
Keyword(s):  
High Performance ◽  
Biological Activities ◽  
Human Keratinocytes ◽  
Achillea Millefolium ◽  
Protection Factor ◽  
Caffeoylquinic Acid ◽  
Cosmetic Ingredients ◽  
Achillea Biebersteinii ◽  
Bioactive Ingredients ◽  
Diphenolase Activity

Studies on hydroglycolic (HG) extracts of Achillea biebersteinii (AB)—a less investigated representative of the genus—were performed to determine their potential for cosmetic applications compared to the well-known Achillea millefolium (AM). Three types of water:polyethylene glycol extracts (1:1, 4:1, 6:1 v/v) were obtained from both species and analyzed for their composition by high performance liquid chromatography coupled with mass spectrometry (HPLC-ESI-Q-TOF-MS) and assayed for their biological activities. The study led to the identification of 11 metabolites from different natural product classes with the highest share corresponding to 5-caffeoylquinic acid, axillarin, coumaroylquinic acid isomers and 3-caffeoylquinic acid. The highest antiradical capacity in DPPH and ABTS scavenging assays was shown for HG 4:1 of AB and AM extracts. HG 1:1 extracts from both species inhibited monophenolase and diphenolase activity of tyrosinase, whereas AB HG 4:1 extract showed significant monophenolase inhibition. The highest sun protection factor (SPF) was determined for AM HG 4:1 extract, equal to 14.04 ± 0.17. The AB extracts were cytotoxic for both human keratinocytes HaCaT and A375 melanoma, however HG 1:1 and 4:1 extracts were more cytotoxic for cancer than for noncancerous cells. In conclusion, AB HG 1:1 and 4:1 extracts display significant potential as active cosmetic ingredients.

scholarly journals Selective Modulation of Follicle-Stimulating Hormone Signaling Pathways with Enhancing Equine Chorionic Gonadotropin/Antibody Immune Complexes

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2788-2799 ◽  
Author(s):  
Vanessa Wehbi ◽  
Jérémy Decourtye ◽  
Vincent Piketty ◽  
Guillaume Durand ◽  
Eric Reiter ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Biological Activities ◽  
Target Cells ◽  
Pharmacological Properties ◽  
Dairy Goats ◽  
Glycoprotein Hormone ◽  
Guanine Nucleotide Binding Protein ◽  
Equine Chorionic Gonadotropin ◽  
The Impact

The injection of equine chorionic gonadotropin (eCG) in dairy goats induces the production of anti-eCG antibodies (Abs) in some females. We have previously shown that Abs negatively modulate the LH and FSH-like bioactivities of eCG, in most cases, compromising fertility in treated females. Surprisingly, we found out that some anti-eCG Abs improved fertility and prolificity of the treated females, in vivo. These Abs, when complexed with eCG, enhanced LH and FSH ability to induce steroidogenesis on specific target cells, in vitro. In the present study, we analyzed the impact of three eCG/anti-eCG Ab-enhancing complexes on two transduction mechanisms triggered by the FSH receptor: guanine nucleotide-binding protein αS-subunit/cAMP/protein kinase A (PKA) and β-arrestin-dependent pathways, respectively. In all cases, significant enhancing effects were observed on ERK phosphorylation compared with eCG alone. However, cAMP production and PKA activation induced by eCG could be differently modulated by Abs. By using a pharmacological inhibitor of PKA and small interfering RNA-mediated knock-down of endogenous β-arrestin 1 and 2, we demonstrated that signaling bias was induced and was clearly dependent on the complexed Ab. Together, our data show that eCG/anti-eCG Ab-enhancing complexes can differentially modulate cAMP/PKA and β-arrestin pathways as a function of the complexed Ab. We hypothesize that enhancing Abs may change the eCG conformation, the immune complex acquiring new “biased” pharmacological properties ultimately leading to the physiological effects observed in vivo. The modulation of ligand pharmacological properties by Abs opens promising research avenues towards the optimization of glycoprotein hormone biological activities and, more generally, the development of new therapeutics.

scholarly journals Expression of Nef Downregulates CXCR4, the Major Coreceptor of Human Immunodeficiency Virus, from the Surfaces of Target Cells and Thereby Enhances Resistance to Superinfection

2006 ◽  
Vol 80 (22) ◽  
pp. 11141-11152 ◽  
Author(s):  
Stephanie Venzke ◽  
Nico Michel ◽  
Ina Allespach ◽  
Oliver T. Fackler ◽  
Oliver T. Keppler
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocytes ◽  
Maximum Level ◽  
Target Cells ◽  
Class I Mhc ◽  
Mhc I ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Stromal Cell Derived Factor ◽  
Hiv 1

ABSTRACT Lentiviral Nef proteins are key factors for pathogenesis and are known to downregulate functionally important molecules, including CD4 and major histocompatibility complex class I (MHC-I), from the surfaces of infected cells. Recently, we demonstrated that Nef reduces cell surface levels of the human immunodeficiency virus type 1 (HIV-1) entry coreceptor CCR5 (N. Michel, I. Allespach, S. Venzke, O. T. Fackler, and O. T. Keppler, Curr. Biol. 15:714-723, 2005). Here, we report that Nef downregulates the second major HIV-1 coreceptor, CXCR4, from the surfaces of HIV-infected primary CD4 T lymphocytes with efficiencies comparable to those of the natural CXCR4 ligand, stromal cell-derived factor-1 alpha. Analysis of a panel of mutants of HIV-1SF2 Nef revealed that the viral protein utilized the same signature motifs for downmodulation of CXCR4 and MHC-I, including the proline-rich motif P73P76P79P82 and the acidic cluster motif E66E67E68E69. Expression of wild-type Nef, but not of specific Nef mutants, resulted in a perinuclear accumulation of the coreceptor. Remarkably, the carboxy terminus of CXCR4, which harbors the classical motifs critical for basal and ligand-induced receptor endocytosis, was dispensable for the Nef-mediated reduction of surface exposure. Functionally, the ability of Nef to simultaneously downmodulate CXCR4 and CD4 correlated with maximum-level protection of Nef-expressing target cells from fusion with cells exposing X4 HIV-1 envelopes. Furthermore, the Nef-mediated downregulation of CXCR4 alone on target T lymphocytes was sufficient to diminish cells' susceptibility to X4 HIV-1 virions at the entry step. The downregulation of chemokine coreceptors is a conserved activity of Nef to modulate infected cells, an important functional consequence of which is an enhanced resistance to HIV superinfection.

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