Exosome Limitations in the Treatment of Inflammatory Diseases

2020 ◽  
Vol 26 ◽  
Author(s):  
Daria Skuratovskaia ◽  
Maria Vulf ◽  
Olga Khaziakhmatova ◽  
Vladimir Malashchenko ◽  
Aleksandra Komar ◽  
...  

Background: Despite the great interest and numerous studies, there is currently no unified standard describing the sequential manipulation with cells to obtain exosomes for clinical use.The use of exosomes has become an attractive alternative to cell therapy, since the flexible nature of these biological vesicles allows scientists to manipulate their composition to produce the desired exosomes carrying specific drugs, RNA and proteins. This study aimed to analyse scientific literature on the changes in the functional characteristics of exosomes, depending on the method of manipulation, potentially contributing to the development of negative effects in the treatment of diseases of inflammatory genesis Results: The choice of isolation method affects the expressed sets of protein markers, nucleic acids and receptors on microparticles. Various surface receptors present on the exosome membrane can be engineered to target lesions. Exosomes from healthy patients help to reduce inflammation, normalize intercellular communication and have antifibrotic, antioxidant, and cytoprotective effects. Exosomes can change the microenvironment, but the microenvironment can also change the composition of exosomes. Conclusion: Exosomes obtained from sick patients carry markers characteristic of the corresponding disease. Such exosomes can have pro-inflammatory, pro-fibrotic, cytotoxic, and oncogenic properties, and disrupt cellular cooperation. Until now, questions regarding the dose, reactions to repeated administration, and dosage regimes have not been completely resolved.

Author(s):  
M.A. Zemlianova ◽  
I.V. Tikhonova

Alumina refineries are among the leading sources of atmospheric air pollution with a wide range of pollutants hazardous to human respiratory organs. It is relevant to study and evaluate the occurrence of the risks for development of respiratory diseases in children living in the area affected by the emission components of an alumina refinery. We assessed air quality of the area under observation and comparison according to monitoring observations, risk of non-carcinogenic effects from the respiratory organs. The content of chemicals in the blood and urine adequate to risk factors was quantified. The structure of individual groups of respiratory diseases was analyzed. The causal relationships of violations of laboratory parameters with an increased content of chemicals in biological media were evaluated. It was found that an aerogenic exposure of chemical pollutants is formed on the territory with the production of metallurgical alumina. It determines the risk for development of respiratory diseases, exceeding an acceptable level up to 49.9 times. In the exposed children, the content of manganese, chromium, nickel, copper, xylenes, formaldehyde and aluminum, fluoride ion in the urine was increased to 4.2 times in relation to the indices in the comparison group. A high level of additional respiratory morbidity(1.8 times) was revealed. Chronic lymphoproliferative diseases of the nasopharynx and inflammatory diseases of the upper respiratory tract (up to 6.6 times more often), inflammatory diseases with a predominance of the mechanism of allergic inflammation ( up to 2.1 times more often)are more often detected in the framework of the respiratory diseases. Negative effects on the part of the respiratory system in the form of activation of antioxidant processes, the development of an inflammatory reaction, local, general and specific sensitization of the respiratory tract were established. It confirms the occurrence of the risks for the development of respiratory diseases in children in the exposure area of the chemical factors of alumina refinery-associated economic activity.


Entropy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. 616
Author(s):  
Marek Berezowski ◽  
Marcin Lawnik

Research using chaos theory allows for a better understanding of many phenomena modeled by means of dynamical systems. The appearance of chaos in a given process can lead to very negative effects, e.g., in the construction of bridges or in systems based on chemical reactors. This problem is important, especially when in a given dynamic process there are so-called hidden attractors. In the scientific literature, we can find many works that deal with this issue from both the theoretical and practical points of view. The vast majority of these works concern multidimensional continuous systems. Our work shows these attractors in discrete systems. They can occur in Newton’s recursion and in numerical integration.


2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.


1992 ◽  
Vol 3 (suppl b) ◽  
pp. 11-19
Author(s):  
Charles A Dinarello

Treating the septic shock syndrome with antibodies that block only endotoxin has its limitations. Other targets for treating septic shock include neutralizing antibodies to the complement fragment C5a, platelet activating factor antagonists and blockade of endothelial cell leukocyte adhesion molecules. Specific blockade of the pro-inflammatory cytokines interleukin-1 (IL-1) or tumour necrosis factor (TNF) reduces the morbidity and mortality associated with septic shock. Moreover, blocking IL-1 and TNF likely has uses in treating diseases other than septic shock. Use of neutralizing antibodies to TNF or IL-1 receptors has reduced the consequences of infection and inflammation, including lethal outcomes in animal models. The IL-1 receptor antagonist, a naturally occurring cytokine, blocks shock and death due to Escherichia coli as well as ameliorates a variety of inflammatory diseases. Soluble TNF and IL-1 surface receptors, which bind their respective cytokines. also ameliorate disease processes. Clinical trials are presently evaluating the safety and efficacy of anticytokine therapies either alone or in combination.


2004 ◽  
Vol 286 (1) ◽  
pp. G76-G81 ◽  
Author(s):  
John L. Wallace ◽  
Stella R. Zamuner ◽  
Webb McKnight ◽  
Michael Dicay ◽  
Andrea Mencarelli ◽  
...  

Aceylation of cyclooxygenase (COX)-2 by aspirin can trigger the formation of 15(R)-epilipoxin A4, or aspirin-triggered lipoxin (ATL). ATL exerts protective effects in the stomach. Selective COX-2 inhibitors block ATL synthesis and exacerbate aspirin-induced gastric damage. Nitric oxide-releasing aspirins, including NCX-4016, have antiplatelet effects similar to aspirin but do not cause gastric damage. In the present study, we examined whether or not NCX-4016 triggers ATL synthesis and/or upregulates gastric COX-2 expression and the effects of coadministration of NCX-4016 with a selective COX-2 inhibitor on gastric mucosal injury and inflammation. Rats were given aspirin or NCX-4016 orally and either vehicle or a selective COX-2 inhibitor (celecoxib) intraperitoneally. Gastric damage was blindly scored, and granulocyte infiltration into gastric tissue was monitored through measurement of myeloperoxidase activity. Gastric PG and ATL synthesis was measured as was COX-2 expression. Whereas celecoxib inhibited gastric ATL synthesis and increased the severity of aspirin-induced gastric damage and inflammation, coadministration of celecoxib and NCX-4016 did not result in damage or inflammation. NCX-4016 did not upregulate gastric COX-2 expression nor did it trigger ATL synthesis (in contrast to aspirin). Daily administration of aspirin for 5 days resulted in significantly less gastric damage than that seen with a single dose, as well as augmented ATL synthesis. Celecoxib reversed this effect. In contrast, repeated administration of NCX-4016 failed to cause gastric damage, whether given alone or with celecoxib. These studies support the notion that NCX-4016 may be an attractive alternative to aspirin for indications such as cardioprotection, including in individuals also taking selective COX-2 inhibitors.


2010 ◽  
Vol 34 (4) ◽  
pp. 1103-1112 ◽  
Author(s):  
Rubens José Campo ◽  
Ricardo Silva Araujo ◽  
Fábio Luís Mostasso ◽  
Mariangela Hungria

Soybean is a major grain crop in Brazil, and yields can be considerably improved by inoculation with selected Bradyrhizobium strains. However, the incompatibility between inoculation and seed treatments with fungicides and micronutrients represents a major barrier to the achievement of high rates of biological N2 fixation. Inoculation practices that can alleviate the negative effects of agrochemicals must therefore be found and in-furrow inoculation seems to be an attractive alternative. This study reports the results of seven field experiments conducted in three growing seasons in Brazil; three in soils previously cropped with inoculated soybean (> 10(4) cells g-1 of soil of Bradyrhizobium), and four in areas where the crop was sown for the first time (< 10² cells g-1 of soil of Bradyrhizobium). The compatibility with fungicides and micronutrients was compared in seeds inoculated with peat or liquid inoculants, or treated with different doses of liquid inoculant in-furrow. In areas with established Bradyrhizobium populations, seed-applied agrochemicals did generally not affect nodulation, but also did not increase yields, while inoculation always increased N grain accumulation or yield, and N fertilizer decreased both nodulation and yield. Where soybean was sown for the first time, the seed treatment with agrochemicals affected nodulation when applied together with peat or liquid inoculant. In-furrow inoculation alleviated the effects of seed treatment with agrochemicals; the best performance was achieved with high Bradyrhizobium cell concentrations, with up to 2.5 million cells seed-1.


2002 ◽  
Vol 36 (5) ◽  
pp. 776-780 ◽  
Author(s):  
David A Geier ◽  
Mark R Geier

BACKGROUND: A previous study suggested that high concentrations of endotoxin may be present in whole-cell diphtheria/tetanus/pertussis (DTP) vaccine, and the scientific literature contains many studies examining the reactivity of whole-cell DTP vaccine. The medical and scientific communities have previously reported that the presence of endotoxin in commercial vaccines may have negative effects on vaccine recipients. OBJECTIVE: To determine the endotoxin concentrations in whole-cell DTP, acellular DTP (DTaP), and DT vaccines and determine the clinical experience with each vaccine. METHODS: To study the endotoxin concentrations in vaccines, the Limulus amebocyte lysate (LAL) assay was used. The vaccines analyzed with the LAL assay were whole-cell DTP vaccine lots manufactured by Connaught, Lederle, the Michigan and Massachusetts Departments of Health, and Wyeth; DTaP vaccine lots manufactured by Merieux and Takeda; and DT vaccine lots manufactured by Wyeth and Lederle. The incidence of adverse reactions following whole-cell DTP, DTaP, and DT vaccines were determined based on analysis of the Vaccine Adverse Events Reporting System (VAERS) database. RESULTS: The results of the LAL assay showed that whole-cell DTP vaccines contained considerably more endotoxin than either DTaP or DT vaccines. The VAERS showed that statistically significantly more adverse reactions were associated with whole-cell DTP vaccine than DTaP or DT vaccines. CONCLUSIONS: This analysis confirmed higher concentrations of endotoxin in whole-cell DTP vaccines compared with DTaP or DT vaccines. As high concentrations of endotoxin may be correlated with a higher incidence of adverse events, the switch from whole-cell DTP to DTaP for routine vaccinations in the US seems well justified.


Author(s):  
Guenther Maier

Globalization and digitalization have yielded new challenges in the B2B sales environment. Besides positive also negative effects appeared in the last decades. Customer behaviour is becoming more complex, and the rivalry between the firms is getting more aggressive. Especially product-centred firms strive to fulfil their financial targets. The actual situation of COVID-19 amplify this situation. This new challenge entails firms and salespeople to find new resilient ways to survive and overcome crisis’s and resist the rivalry of competitors. The present article is based on the theoretical and extant literature of solution selling and customer solutions in different industries. Potential effects on solution selling will be discussed and contributed through empirical interviews with people in a leadership position in sales. This article analyses the individual perception of related stakeholders in B2B sales and will provide valuable insights on solution selling concerning their resilient attribute. This present review will contribute scholars on the existing literature and firms which are seeking for methods to distinct from competitors and to overcome crisis´s. Finally, the gaps in the scientific literature will be discussed for further research.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yifan Qu ◽  
Xinyi Li ◽  
Fengying Xu ◽  
Shimin Zhao ◽  
Xuemei Wu ◽  
...  

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)–dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.


2021 ◽  
Vol 162 (3) ◽  
pp. 83-90
Author(s):  
Árpád Farkas ◽  
Gábor Tomisa ◽  
Erika Kis ◽  
Alpár Horváth

Összefoglaló. A dohányzás káros hatásainak vizsgálata hosszú ideje az orvostudomány egyik legintenzívebben kutatott területe. A nagy tudományos érdeklődésnek köszönhetően ma már meggyőző evidenciák állnak rendelkezésre a hagyományos cigaretta használatának számos negatív hatásáról. Ezzel ellentétben a sokkal később bevezetett helyettesítő termékek veszélyeiről lényegesen kevesebbet tudunk. E körbe tartozik a manapság egyre népszerűbb elektromos cigaretta is, amelyre egyre több, egészségügyi kockázatot felmérő munka fókuszál. Ugyanakkor a több évszázados múltra visszatekintő és a világ bizonyos helyein sokáig népszerű vízipipa érdekes esetnek számít, mivel használóinak száma a nyugati világban az utóbbi időben megugrott, de az emberre gyakorolt hatása számos ponton még vita tárgyát képezi. A jelen munka célja, hogy a hazai és a nemzetközi szakirodalom alapján feltérképezze a hagyományos cigaretta, az elektromos cigaretta és a vízipipa fontosabb egészségügyi hatásait, és rámutasson azokra a kapcsolódó területekre, ahol további kutatások szükségesek. A szakirodalmi áttekintés során a különböző publikációs adatbázisokban fellelhető tudományos cikkeket elemeztük. A megvizsgált szakirodalom alapján a tartós dohányzásnak bizonyítottan a szív-ér rendszert és a légzőrendszert károsító hatása van, de növekvő számú bizonyíték utal a neurológiai káros hatásokra és a gasztroenterológiai hatásokra is. Ugyanakkor az elektromos cigaretta és a vízipipa esetében a bizonyított akut hatások mellett a hosszú távú hatásokat illetően további intenzív kutatásokra van szükség. Az elektromos cigaretta és a vízipipa esetében a hosszú távú hatások kapcsán a meggyőző evidencia hiánya semmiképpen nem jelenti azt, hogy ezen termékeket kockázatmentesnek kellene tekinteni, sőt a pulmonológusoknak és a döntéshozóknak mindent meg kell tenniük annak érdekében, hogy valamennyi dohánytermék törvényi szabályozása azok használatának visszaszorítását célozza. A kérdés fontosságának a COVID–19-pandémia különös aktualitást ad. Orv Hetil. 2021; 162(3): 83–90. Summary. Revealing the health effects associated with smoking has been in the focus of intense research for decades. Due to these research efforts, there is a convincing evidence regarding the negative effects of conventional cigarettes. However, much less is known about the replacement products such as electronic cigarettes. Moreover, the effects of waterpipes are also not fully explored, in spite of their long history. The scope of the present work is to survey the open literature to map the knowledge related to the health effects of conventional cigarettes, e-cigarettes and waterpipes. The analysis of the related scientific literature was performed based on papers retrieved in large publication repositories. Based on the reviewed literature, long-term smoking has demonstrated adverse effects on the respiratory as well as the heart and circulatory systems. In addition, the correlation between cigarette smoking and some gastroenterological and neurological diseases is also increasingly evident. By the same token, though the acute effects of e-cigarette and waterpipe are well documented, the protracted effects are still to be explored. The lack of pertinent information regarding the late effects of e-cigarette and hookah does not imply that there is no health risk associated with their consumption. On the contrary, in addition to the regular antismoke measures, pulmonologists and policy makers should do everything to lower the consumption of these alternative products. Orv Hetil. 2021; 162(3): 83–90.


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