scholarly journals Application of Exosomes-Derived Mesenchymal Stem Cells in Treatment of Fungal Diseases: From Basic to Clinical Sciences

2021 ◽  
Vol 2 ◽  
Author(s):  
Seyedeh Ommolbanin Ghasemian

Fungal diseases such as candidiasis are some of the deadliest diseases among immunocompromised patients. These fungi naturally exist on human skin and throughout the digestive system. When the microbiota balance becomes upset, these fungi become pathogenic and potentially lethal. At the pathogenesis of fungal diseases, host immune system response is diverse. At the early stages of fungal pathogenesis such as Candida albicans, it was shown that these fungi use the immune cells of the host body and cause malfunction the early induction of proinflammatory cytokines of the host body leading to a reduction in their numbers. However, at some stages of fungal diseases, the immune response is severe. Despite many treatments already being available, it seems that one of the best treatments could be an immune-stimulatory agent. Some of the subsets of MSCs and exosome-derived cells, as a cell-to-cell communicator agent, have many roles in the human body, including anti-inflammatory and immune-modulatory effects. However, the TLR4-primed and IL-17+ subsets of MSCs have been shown to have immune-stimulatory effects. These subsets of the MSCs produce pro-inflammatory cytokines and reduce immunosuppressive cytokines and chemokines. Thus, they could trigger inflammation and stop fungal pathogenesis. As some biological activities and molecules inherit elements of their exosomes from their maternal cells, the exosome-derived TLR4-primed and IL-17+ subsets of MSCs could be a good candidate for fighting against fungal diseases. The applications of exosomes in human diseases are well-known and expanding. It is time to investigate the exosomes application in fungal diseases. In this review, the probable role of exosomes in treating fungal diseases is explored.

2007 ◽  
Vol 85 (5) ◽  
pp. 552-562 ◽  
Author(s):  
Brian J. Hillier ◽  
Victor D. Vacquier

Amassin-1 mediates a rapid cell adhesion that tightly adheres sea urchin coelomocytes (body cavity immunocytes) together. Three major structural regions exist in amassin-1: a short β region, 3 coiled coils, and an olfactomedin domain. Amassin-1 contains 8 disulfide-bonded cysteines that, upon reduction, render it inactive. Truncated forms of recombinant amassin-1 were expressed and purified from Pichia pastoris and their disulfide bonding and biological activities investigated. Expressed alone, the olfactomedin domain contained 2 intramolecular disulfide bonds, existed in a monomeric state, and inhibited amassin-1-mediated clotting of coelomocytes by a calcium-dependent cell-binding activity. The N-terminal β region, containing 3 cysteines, was not required for clotting activity. The coiled coils may dimerize amassin-1 in a parallel orientation through a homodimerizing disulfide bond. Neither amassin-1 fragments that were disulfide-linked as dimers or that were engineered to exist as dimers induced coelomocytes clotting. Clotting required higher multimeric states of amassin-1, possibly tetramers, which occurred through the N-terminal β region and (or) the first segment of coiled coils.


2021 ◽  
Author(s):  
A.E. Manukyan ◽  
A.A. Hovhannisyan

ABSTRACTThe cyclooxygenase (COX) enzymes are tumor markers, the inhibition of which can be used in the prevention and therapy of carcinogenesis. It was found that COX-2 IS considered as targets for tumor inhibition. Aminopeptidase N (APN) is a type II membrane-bound metalloprotease associated with cancer, being identified as a cell marker on the surface of malignant myeloid cells and reached a high level of expression in progressive tumors. In anticancer therapy, plant compounds are considered that can inhibit their activity. Modeling of the COX-2 and APN enzymes was carried out on the basis of molecular models of three-dimensional structures from the PDB database [PDB ID: 5f19, 4fyq] RCSB. For docking analysis, 3D ligand models were created using MarvinSketch based on the PubChem database [CID: 5280343, 5281654]. In silico experiments, for the first time, revealed the possible interaction and inhibition of COX-2 and APN by quercetin and quercetin derivatives. Aspirin and Marimastat were taken to compare the results. Possible biological activities and possible side effects of the ligands have been identified.


2016 ◽  
Vol 52 (26) ◽  
pp. 4757-4760 ◽  
Author(s):  
Min Kyung Lee ◽  
Jooyeon Park ◽  
Xuefeng Wang ◽  
Mehdi Roein-Peikar ◽  
Eunkyung Ko ◽  
...  

Hydrogels coupled with integrin-binding deoxyribonucleic acid (DNA) tethers with pre-defined rupture forces can modulate phenotypic activities of stem cells.


2007 ◽  
Vol 76 (1) ◽  
pp. 127-140 ◽  
Author(s):  
Kanhu C. Mishra ◽  
Chantal de Chastellier ◽  
Yeddula Narayana ◽  
Pablo Bifani ◽  
Alistair K. Brown ◽  
...  

ABSTRACT PE and PPE proteins appear to be important for virulence and immunopathogenicity in mycobacteria, yet the functions of the PE/PPE domains remain an enigma. To decipher the role of these domains, we have characterized the triacylglycerol (TAG) hydrolase LipY from Mycobacterium tuberculosis, which is the only known PE protein expressing an enzymatic activity. The overproduction of LipY in mycobacteria resulted in a significant reduction in the pool of TAGs, consistent with the lipase activity of this enzyme. Unexpectedly, this reduction was more pronounced in mycobacteria overexpressing LipY lacking the PE domain [LipY(ΔPE)], suggesting that the PE domain participates in the modulation of LipY activity. Interestingly, Mycobacterium marinum contains a protein homologous to LipY, termed LipYmar, in which the PE domain is substituted by a PPE domain. As for LipY, overexpression of LipYmar in Mycobacterium smegmatis significantly reduced the TAG pool, and this was further pronounced when the PPE domain of LipYmar was removed. Fractionation studies and Western blot analysis demonstrated that both LipY and LipY(ΔPE) were mainly present in the cell wall, indicating that the PE domain was not required for translocation to this site. Furthermore, electron microscopy immunolabeling of LipY(ΔPE) clearly showed a cell surface localization, thereby suggesting that the lipase may interact with the host immune system. Accordingly, a strong humoral response against LipY and LipY(ΔPE) was observed in tuberculosis patients. Together, our results suggest for the first time that both PE and PPE domains can share similar functional roles and that LipY represents a novel immunodominant antigen.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Gianfranco Lauletta ◽  
Sabino Russi ◽  
Vincenza Conteduca ◽  
Loredana Sansonno

Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic B-cell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures.


2002 ◽  
Vol 57 (3-4) ◽  
pp. 319-322 ◽  
Author(s):  
Kolishka Tsekova ◽  
Dessislava Todorova

The influence of copper (II) ions on the growth, accumulation properties and superoxide dismutase (SOD) activity of a growing culture of Aspergillus niger B-77 were studied. Microbial growth, the level of copper (II) accumulation and SOD activity depended on the initial copper (II) concentration. Aspergillus niger is able to accumulate large amounts of copper (II) from the nutrient medium with 200 mg.l-1 copper (II) ions without loosing its biological activities. Addition of copper (II) ions increased the SOD activity in the growing cell cultures. The changes in enzyme activity induced by heavy metal ions might be used as an indicator of intracellular oxy-intermediate generation in a cell culture growing under stress conditions


2009 ◽  
Vol 18 (5-6) ◽  
pp. 677-682 ◽  
Author(s):  
Yoshitaka Miyamoto ◽  
Takeshi Ikeya ◽  
Shin Enosawa

Three-dimensional culture procedures have attracted attention in various fields of cell biology. A newly developed cell array assisted in the formation of hepatocyte spheroids by two innovations: 1) micropatterning by a hydrophilic polymer, and 2) the use of bovine carotid artery-derived HH cells as feeder cells. The former contributes to the standardization of the spheroid size and the latter to the maintenance of the spheroids. We created a way to provide a ready-to-use cell array by cryopreservation of an HH feeder cell cultured array. After inoculation of HH cells on the cell array, the culture medium was replaced by freezing medium containing dimethyl sulfoxide. Thereafter, the array was frozen and stored in a −80°C deep freezer. At the start of the hepatocyte culture, the cryopreserved HH cell array was thawed by adding warmed (37°C) culture medium. The morphology and biological activities of the cryopreserved HH cells were intact, as confirmed by phase contrast microscopy and functional staining with calcein and formazan. The rat hepatocytes formed perfect spheroids on the cryopreserved HH cell array without any differences from those on the freshly prepared HH cell array. The CYP3A drug metabolism activities of the hepatocytes were well maintained on the cryopreserved and fresh cell arrays. The present protocol greatly shortened the time and labor required to prepare a cell array for culturing hepatocytes.


mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Luna S. Joffe ◽  
Leonardo Nimrichter ◽  
Marcio L. Rodrigues ◽  
Maurizio Del Poeta

ABSTRACT Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Additionally, recent studies have demonstrated that fungal EVs stimulate the host immune system. In this review, putative roles of fungal EVs are discussed, including their potential as vaccination tools and their possible contribution to pathogenesis in invasive fungal diseases.


2013 ◽  
Vol 3 (5) ◽  
pp. 154 ◽  
Author(s):  
Jing-Xin Ma ◽  
Hong Li ◽  
Xiao-Xin Cheng ◽  
Mo-Li Wu ◽  
Li-Jun Yu ◽  
...  

Backgrounds: Medulloblastoma (MB) is the commonest brain malignancy in childhood with poor prognosis, because of its rapid aggressive growth and frequent occurrence. The current chemotherapeutic regimens for medulloblastoma patients involve a combination of lomustine, cisplatin, carboplatin, vincristine or cyclophosphamide, which have distinct short- and long-term side-effects. It is therefore in urgent need to explore safer and more effective adjuvant approach(s). Resveratrol, a polyphenol rich in numerous plants, has multiple biological activities including anticancer effects. Our previous data confirmed that resveratrol inhibited proliferation and induced differentiation and apoptosis of medulloblastoma cells. SIRT1 is a deacetylase of class III HDACs and the supposed molecular effecter of resveratrol. SIRT1 involves in aging prevention and cancer formation in a cell-context specific manner. Nevertheless, the datum concerning the role(s) of SIRT1 in formation and prognosis of medulloblastoma is still missing.Objective: The present study aimed to address the expression patterna of SIRT1 in medulloblastoma tissues and non-cancerous counterparts and to explore whether resveratrol exerts its anti-medulloblastoma effects via regulating SIRT1 expression and bioactivity.Methods: The expression of SIRT1 in medulloblastoma and non-cancerous counterparts was elucidated by immunohistochemical ataining (IHC). To clarify the function of SIRT1 in medulloblastomas, SIRT1 expression in UW228-3 medulloblastoma cells were suppressed by RNA interference (RNAi). The influence of resveratrol in SIRT1 expressions in UW228-3 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry (ICC) and Western blotting (WB). The catalytic activity of deacetylase SIRT1 was examined by measuring the acetylation of the main substrate p53.Results: IHC staining revealed that SIRT1 was expressed in 64.17% of MB tissues, which was higher than that in noncancerous cerebellum tissues (14.29%). The frequencies of SIRT1 expression in the nodular MB (22.22%) with better prognosis is lower than that in anaplastic MB (79.07% ) and classic MB (60.29 %; P<0.05). The proliferation of UW228-3 cells was remarkably suppressed after being transfected with SIRT1 siRNA, accompanied with extensive cell death. The results of RT-PCR and WB showed that after 48 hours 100 M resveratrol treatment, SIRT1 expression in UW228-3 cells was down-regulated at both transcriptional and translational levels. However, resveratrol has no effect on the deacetylase activity of SIRT1.Conclusion: The above findings suggested that SIRT1 expression is corrected with the formation and prognosis of human MB. Resveratrol influences SIRT1 functioning in human MB cells through inhibiting SIRT1 expression rather than modulating its acetylation activity.Keywords: resveratrol, SIRT1, RNA interference, deacetylase, medulloblastoma


Author(s):  
MAURICIO REGINALDO ALVES DOS SANTOS ◽  
CAROLINA SOUZA

In vitro cell suspension cultivation systems have been largely reported as safe and standardized methods for production of secondary metabolites with medicinal and agricultural interest. Capsicum annuum is one of the most widely grown vegetable in the world and its biological activities have been demonstrated against insects, fungi, bacteria and other groups of organisms. The determination of procedures for the dedifferentiation of cells into callus cells and the subsequent study of the callus growth pattern are necessary for the establishment of cell suspensions and also to subsidize studies regarding the bioactivity of its secondary metabolites. The objective of this study was to establish a protocol for dedifferentiation of leaf cells of the cultivar C. annuum cv. Etna and to determine the growth pattern of the calluses with a focus on the deceleration phase, when the callus cells must be subcultured into a liquid medium in order to establish cell suspension cultivations aiming at the production of secondary metabolites. treatment that resulted in the highest %CI, ACCC and callus weight was the combination of 4.52 µM 2,4-D + 0.44 µM BA. The calluses produced were friable and whitish and their growth pattern followed a sigmoid shape. The deceleration phase started on the 23rd day of cultivation. Callus induction in leaf explants of C. annuum cv. Etna can be achieved in MS medium supplemented with 4.52 µM 2,4-D + 0.44 µM BA, which results in high cellular proliferation; in order to start a cell suspension culture, callus cells on the 23rd day of culture should be used.


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