scholarly journals Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors

2020 ◽  
Vol 21 (23) ◽  
pp. 9055
Author(s):  
Mahmoud Mona ◽  
Firas Kobeissy ◽  
Yun-Jong Park ◽  
Rehae Miller ◽  
Wafaa Saleh ◽  
...  

Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries.

2019 ◽  
Vol 20 (3) ◽  
pp. 767 ◽  
Author(s):  
Mahmoud Mona ◽  
Rehae Miller ◽  
Hui Li ◽  
Yun-Jong Park ◽  
Raafi Zaman ◽  
...  

Sjögren’s syndrome (SjS) is an autoimmune disease that destroys the salivary glands and results in severe dry mouth. Mesenchymal stem cell (MSC) transplantation has been recently proposed as a promising therapy for restoring cells in multiple degenerative diseases. We have recently utilized advanced proteomics biochemical assays to identify the key molecules involved in the mesenchymal-epithelial transition (MET) of co-cultured mouse bone-marrow-derived MSCs mMSCs with primary salivary gland cells. Among the multiple transcription factors (TFs) that were differentially expressed, two major TFs were selected: muscle, intestine, and stomach expression-1 (MIST1) and transcription factor E2a (TCF3). These factors were assessed in the current study for their ability to drive the expression of acinar cell marker, alpha-salivary amylase 1 (AMY1), and ductal cell marker, cytokeratin19 (CK19), in vitro. Overexpression of MIST1-induced AMY1 expression while it had little effect on CK19 expression. In contrast, TCF3 induced neither of those cellular markers. Furthermore, we have identified that mMSCs express muscarinic-type 3 receptor (M3R) mainly in the cytoplasm and aquaporin 5 (AQP5) in the nucleus. While MIST1 did not alter M3R levels in mMSCs, a TCF3 overexpression downregulated M3R expressions in mMSCs. The mechanisms for such differential regulation of glandular markers by these TFs warrant further investigation.


2015 ◽  
Vol 89 (18) ◽  
pp. 9499-9510 ◽  
Author(s):  
Bo Liang ◽  
Sonja Surman ◽  
Emerito Amaro-Carambot ◽  
Barbora Kabatova ◽  
Natalie Mackow ◽  
...  

ABSTRACTRespiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response.IMPORTANCERespiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation.


Author(s):  
Evgeny Kharin ◽  
Olga Belykh

In the context of the development of infrastructure in Siberian cities, the issues of the state of the areas with accumulated environmental damage is especially relevant. It is mentioned in the article that lichen indication is an efficient method of passive monitoring of environment for industrial pollutants caused by morphological changes occurring in sensitive objects. The results of the lichen floristic research of Leninsky district of Irkutsk are presented, a list of revealed lichens including 9 genera and 12 species is given, a taxonomic list of this area is discussed. Lichenological objects were mapped. Distribution of lichens in the area of research is investigated with regard to the presence of recreational and residential zones. The authors draw a conclusion about the presence of «lichens deserts» which are caused both by the absence of the respective substratum and high concentration of pollutants. High concentration of pollutants is caused by complex influence of different enterprises on the quality of air.


1995 ◽  
Vol 109 (5) ◽  
pp. 466-468 ◽  
Author(s):  
Bonnie L. Kemp ◽  
John G. Batsakis ◽  
Adel K. El-Naggar ◽  
Sophia N. Kotliar ◽  
Mario A. Luna

AbstractThe major salivary glands are considered to rarely be the sites of primary terminal duct adenocarcinomas, a neoplasm with a considerable predilection for origin from intraoral minor salivary glands. We present a clinicopathological study of 22 terminal duct adenocarcinomas of the parotid gland, the largest single series to date. A comparison between the parotid neoplasms and over 200 minor salivary gland terminal duct adenocarcinomas indicates there is little difference in biological behaviour and confirms the low-grade quality of the carcinomas, regardless of site of origin.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Hyun-Jeong Lee ◽  
Hye-Sun Park ◽  
Woonsu Kim ◽  
Duhak Yoon ◽  
Seongwon Seo

The interrelationship between muscle and adipose tissues plays a major role in determining the quality of carcass traits. The objective of this study was to compare metabolic differences between muscle and intramuscular adipose (IMA) tissues in thelongissimus dorsi(LD) of Hanwoo (Bos taurus coreanae) using the RNA-seq technology and a systems biology approach. The LD sections between the 6th and 7th ribs were removed from nine (each of three cows, steers, and bulls) Hanwoo beef cattle (carcass weight of430.2±40.66 kg) immediately after slaughter. The total mRNA from muscle, IMA, and subcutaneous adipose and omental adipose tissues were isolated and sequenced. The reads that passed quality control were mapped onto the bovine reference genome (build bosTau6), and differentially expressed genes across tissues were identified. The KEGG pathway enrichment tests revealed the opposite direction of metabolic regulation between muscle and IMA. Metabolic gene network analysis clearly indicated that oxidative metabolism was upregulated in muscle and downregulated in IMA. Interestingly, pathways for regulating cell adhesion, structure, and integrity and chemokine signaling pathway were upregulated in IMA and downregulated in muscle. It is thus inferred that IMA may play an important role in the regulation of development and structure of the LD tissues and muscle/adipose communication.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249470
Author(s):  
Mauro Contini ◽  
Antonio Sarmento ◽  
Paola Gugliandolo ◽  
Alessandra Leonardi ◽  
Gianluigi Longinotti-Buitoni ◽  
...  

Background Ventilation monitoring during sleep is performed by sleep test instrumentation that is uncomfortable for the patients due to the presence of the flowmeter. The objective of this study was to evaluate if an innovative type 3 wearable system, the X10X and X10Y, is able to correctly detect events of apnea and hypopnea and to classify the severity of sleep apnea without the use of a flowmeter. Methods 40 patients with sleep disordered breathing were analyzed by continuous and simultaneous recording of X10X and X10Y and another certified type 3 system, SOMNOtouch, used for comparison. Evaluation was performed in terms of quality of respiratory signals (scores from 1, lowest, to 5, highest), duration and classification of apneas, as well as identification and duration of hypopneas. Results 580 periods were evaluated. Mean quality assigned score was 3.37±1.42 and 3.25±1.35 for X10X and X10Y and SOMNOtouch, respectively. The agreement between the two systems was evaluated with grades 4 and 5 in 383 out of 580 cases. A high correlation (r2 = 0.921; p<0.001) was found between the AHI indexes obtained from the two systems. X10X and X10Y devices were able to correctly classify 72.3% of the obstructive apneas, 81% of the central apneas, 61.3% of the hypopneas, and 64.6% of the mixed apneas when compared to SOMNOtouch device. Conclusion The X10X and X10Y devices are able to provide a correct grading of sleep respiratory disorders without the need of a nasal cannula for respiratory flow measurement and can be considered as a type 3 sleep test device for screening tests.


Author(s):  
Ishtiaque Ahammad

Axon guidance is a crucial process for growth of the central and peripheral nervous systems. In this study, 3 axon guidance related disorders, namely- Duane Retraction Syndrome (DRS) , Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) and Congenital fibrosis of the extraocular muscles type 3 (CFEOM3) were studied using various Systems Biology tools to identify the genes and proteins involved with them to get a better idea about the underlying molecular mechanisms including the regulatory mechanisms. Based on the analyses carried out, 7 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with DRS, HGPPS and CFEOM3 associated genes. From the PPI network, 3 have been identified as hub proteins- DRD2, UBC and CUL3.


2010 ◽  
Vol 37 (No. 1) ◽  
pp. 27-33 ◽  
Author(s):  
P. Jadrná ◽  
O. Plavcová ◽  
F. Kobza

Polyploids were effectively pre-selected in colchicine-treated plants of the desirable brown-leaved cultivar Black Velvet Scarlet F1 of the species <I>Pelargonium × hortorum</I> L.H. Bailey to obtain the basic breeding material for creating new brown-leaved tetraploid cultivars. The green-leaved cultivar Gizela F1 was used for comparison of quantity and quality of response to colchicine treatments. Water solutions of colchicine in the range from 0.1% to 2.5% induced polyploidy in seedlings with treatments repeated each day for 2, 3, 5 or 7 days. Polyploid plants were pre-selected according to their morphological changes and stomata length and density and verified using flow cytometry. Some morphological changes (leaf coloration, flower shapes) in colchiploids differed between the genotypes, others were the same in both cultivars (loss of coloration in mixoploids, failure of blooming).


2018 ◽  
Vol 40 ◽  
pp. 04006
Author(s):  
Kohji Michioku ◽  
Yuki Osawa ◽  
Keiichi Kanda

In a middle stream reach, irreversible morphological changes are observed such as growth of a huge sandbar in front of the confluence, thalweg migration from the left to right bank, erosion of the main channel and sedimentary deposit on the floodplain. As a countermeasure against such degradation of river morphology, a groyne was constructed beneath the tributary confluence. Performance of a groyne in controlling flood flow, sediment transport and river morphology was investigated by a twodimensional hydrodynamic model. The analysis on twenty years of morphological change indicates that the groyne has an excellent performance in improving quality of river morphology such as reduction of the sandbar development and migration of the thalweg to the original position.


2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Md. Hafij Ullah ◽  
James Hazelton ◽  
Peter F Nelson

PurposeThis paper furthers research into the potential contribution of pollutant databases for corporate accountability. We evaluate the quality of corporate and government mercury reporting via the Australian National Pollutant Inventory (NPI), which underpins Australia's reporting under the Minamata Convention, a global agreement to reduce mercury pollution.Design/methodology/approachThe qualitative characteristics of accounting information are used as a theoretical frame to analyse ten interviews with thirteen interviewees as well as 54 submissions to the 2018 governmental enquiry into the NPI.FindingsWhile Australian mercury accounting using the NPI is likely sufficient to meet the expected Minamata reporting requirements (especially in comparison to developing countries), we find significant limitations in relation to comparability, accuracy, timeliness and completeness. These limitations primarily relate to government (as opposed to industry) deficiencies, caused by insufficient funding. The findings suggest that multiple factors are required to realise the potential of pollutant databases for corporate accountability, including appropriate rules, ideological commitment and resourcingPractical implicationsThe provision of additional funding would enable the NPI to be considerably improved (for mercury as well as other pollutants), particularly in relation to the measurement and reporting of emissions from diffuse sources.Originality/valueWhilst there have been prior reviews of the NPI, none have focused on mercury, whilst conversely prior studies which have discussed mercury information have not focused on the NPI. In addition, no prior NPI studies have utilised interviews nor have engaged directly with NPI regulators. There has been little prior engagement with pollutant databases in social and environmental accounting (SEA) research.


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