scholarly journals Investigating CXCR4 expression of tumor cells and the vascular compartment: A multimodal approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260186
Author(s):  
Marta Braga ◽  
Chee Hau Leow ◽  
Javier Hernandez Gil ◽  
Jin H. Teh ◽  
Laurence Carroll ◽  
...  

The C-X-C chemokine receptor 4 (CXCR4) is G protein-coupled receptor that upon binding to its cognate ligand, can lead to tumor progression. Several CXCR4-targeted therapies are currently under investigation, and with it comes the need for imaging agents capable of accurate depiction of CXCR4 for therapeutic stratification and monitoring. PET agents enjoy the most success, but more cost-effective and radiation-free approaches such as ultrasound (US) imaging could represent an attractive alternative. In this work, we developed a targeted microbubble (MB) for imaging of vascular CXCR4 expression in cancer. A CXCR4-targeted MB was developed through incorporation of the T140 peptide into the MB shell. Binding properties of the T140-MB and control, non-targeted MB (NT-MB) were evaluated in MDA-MB-231 cells where CXCR4 expression was knocked-down (via shRNA) through optical imaging, and in the lymphoma tumor models U2932 and SuDHL8 (high and low CXCR4 expression, respectively) by US imaging. PET imaging of [18F]MCFB, a tumor-penetrating CXCR4-targeted small molecule, was used to provide whole-tumor CXCR4 readouts. CXCR4 expression and microvessel density were performed by immunohistochemistry analysis and western blot. T140-MB were formed with similar properties to NT-MB and accumulated sensitively and specifically in cells according to their CXCR4 expression. In NOD SCID mice, T140-MB persisted longer in tumors than NT-MB, indicative of target interaction, but showed no difference between U2932 and SuDHL8. In contrast, PET imaging with [18F]MCFB showed a marked difference in tumor uptake at 40–60 min post-injection between the two tumor models (p<0.05). Ex vivo analysis revealed that the large differences in CXCR4 expression between the two models are not reflected in the vascular compartment, where the MB are restricted; in fact, microvessel density and CXCR4 expression in the vasculature was comparable between U2932 and SuDHL8 tumors. In conclusion, we successfully developed a T140-MB that can be used for imaging CXCR4 expression in the tumor vasculature.

Author(s):  
Sukhbir Lal Khokra ◽  
Sonia Gogat ◽  
Rakesh Narang ◽  
Manish Devgun

Bombax ceiba plant belongs to bombacaceae family and is commonly known as Semal (Hindi) and Cotton tree (English). It has numerous effects like stimulant, astringent, haemostatic, diuretics, antidiarrhoeal, emeticand antipyretic. Major pharmacological activities reported in this plant are hypoglycemic, antianxiety, antibacterial, antiviral and anti-inflammatory. Numerous side effects and increased resistance to anthelmintic drugs prompted us to discover cost effective safe formulation of conventional medicinal plants. In the present study, research work is focused to evaluate the possible anthelmintic effects of Bombax ceiba. To investigate anthelmintic potential of Bombax ceiba plant, different extracts from dried powder stem bark were tested on adult Indian earthworms (Pheretima posthuma) having physiological & anatomical resemblance with human intestinal roundworm parasites. The drugs were divided in 14 groups consisting of test, standard and control. Each group was consisting of six Indian earthworms of approximately same size. Albendazole was used as standard drug while tween80 in normal saline (1:1) was used as control. The result data reveals that all extracts have significant anthelmintic activity as compared to Albendazole taken as standard drug. The methanolic extract at dose of 50 mg/ml concentration showed paralysis time 30±0.96 minutes and death 33.66±0.71 minutes, which is equivalent to standard drug values at dose of 20 mg/ml. Ethylacetate extract at dose of 50 mg/ml showed paralysis at 28.66±0.71 minutes and death at 34.16±1.10 minutes, which proves that it is even better than standard drug in terms of paralysis time and equipotent in terms of time taken for causing death. Thus among the extracts, ethylacetate and methanolic extracts showed maximum activity with least time taken for paralysis and death of earthworms and were found equally potent as Albendazole at a dose of 50 mg/ml. Thus, Bombax ceiba traditional use in helminitic infestation was proved scientifically. On comparing phytochemical evaluation with anthelmintic activity it is assumed that glycosides may be responsible for this activity. A further investigation may lead development of novel anthelmintic drug or formulation with anthelmintic activity.


2020 ◽  
Vol 2020 (3) ◽  
pp. 60408-1-60408-10
Author(s):  
Kenly Maldonado ◽  
Steve Simske

The principal objective of this research is to create a system that is quickly deployable, scalable, adaptable, and intelligent and provides cost-effective surveillance, both locally and globally. The intelligent surveillance system should be capable of rapid implementation to track (monitor) sensitive materials, i.e., radioactive or weapons stockpiles and person(s) within rooms, buildings, and/or areas in order to predict potential incidents proactively (versus reactively) through intelligence, locally and globally. The system will incorporate a combination of electronic systems that include commercial and modifiable off-the-shelf microcomputers to create a microcomputer cluster which acts as a mini supercomputer which leverages real-time data feed if a potential threat is present. Through programming, software, and intelligence (artificial intelligence, machine learning, and neural networks), the system should be capable of monitoring, tracking, and warning (communicating) the system observer operations (command and control) within a few minutes when sensitive materials are at potential risk for loss. The potential customer is government agencies looking to control sensitive materials and/or items in developing world markets intelligently, economically, and quickly.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 716-722
Author(s):  
Sneha Dhakite ◽  
Sadhana Misar Wajpeyi

The “Coronavirus disease 19 (COVID-19)” is caused by “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, a newly discovered member of the Coronaviridae family of viruses which is a highly communicable. There is no effective medical treatment till date for Coronavirus disease hence prevention is the best way to keep disease away. Rasayana proved to be highly efficacious and cost effective for the Prevention and Control of viral infections when vaccines and standard therapies are lacking. Rasayana Chikitsa is one of the eight branches of Ashtanga Ayurveda which helps to maintain healthy life style. Rasayana improves immunity and performs many vital functions of human body. Vyadhikshamatva that is immune mechanism of the body is involved in Prevention of the occurrence of a new disease and it also decreases the virulence and progression of an existing disease. In COVID-19 the Respiratory system mainly get affected which is evident from its symptoms like cold, cough and breathlessness. Here the drugs help in enhancing immune system and strengthening functions of Respiratory system can be useful. For this purpose, the Rasayana like Chyavanprasha, Agastya Haritaki, Pippali Rasayana, Guduchi, Yashtimadhu, Haridra, Ashwagandha, Tulsi are used. Rasayana working on Respiratory system are best for Prevention of Coronavirus and boosting immune system. Rasayana Chikitsa can be effective in the Prevention as well as reducing symptoms of COVID-19.


2020 ◽  
Author(s):  
Jagjit S Soar

he current COVID-19 pandemic now believed to be based on the mutation of the SARS-CoV virus (first reported in 2002) to SARS-CoV-2 emerging in 2019, is naturally causing extreme worry and concern around the world with sometimes mixed and incoherent messages on how to deal with it. There is a plethora of information from previous epidemics caused by other coronaviruses such as severe acute respiratory syndrome, SARS (2002) and Middle East respiratory syndrome MERS (2012) from which we can extrapolate guidance on how to deal with the current pandemic. In the current absence of specific pharmaceutical agents, we propose assessing the extended tools that we already possess in our biological armoury to combat, prevent and control the spread of this virus. Using a set of precise criteria to locate such possible contenders, we conducted literature searches to find compounds that met these criteria. We have now reduced this to a shortlist of three agents that may be the best candidates. We propose vitamin C, vitamin D and Curcumin fit our criteria well. These compounds are widely available to the general public. They are available online and over-the-counter as supplements. Otherwise healthy individuals are safely able to self-administer these agents as a prophylactic to protect themselves and to enhance their immune response. This would be especially desirable for the elderly and at risk groups. These agents can also be used as adjunct therapy, particularly for those who may have early symptoms. This preventative therapy could be implemented whilst awaiting specific pharmaceutical drugs to emerge as a treatment for COVID-19. Our suggested compounds are a highly cost-effective way to potentially reduce the mortality that is regretfully mounting as a result of COVID-19 infection. The biological mode of action and the dosing of these compounds are summarised.


Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3639
Author(s):  
Abdelfateh Kerrouche ◽  
Taoufik Najeh ◽  
Pablo Jaen-Sola

Railway infrastructure plays a major role in providing the most cost-effective way to transport freight and passengers. The increase in train speed, traffic growth, heavier axles, and harsh environments make railway assets susceptible to degradation and failure. Railway switches and crossings (S&C) are a key element in any railway network, providing flexible traffic for trains to switch between tracks (through or turnout direction). S&C systems have complex structures, with many components, such as crossing parts, frogs, switchblades, and point machines. Many technologies (e.g., electrical, mechanical, and electronic devices) are used to operate and control S&C. These S&C systems are subject to failures and malfunctions that can cause delays, traffic disruptions, and even deadly accidents. Suitable field-based monitoring techniques to deal with fault detection in railway S&C systems are sought after. Wear is the major cause of S&C system failures. A novel measuring method to monitor excessive wear on the frog, as part of S&C, based on fiber Bragg grating (FBG) optical fiber sensors, is discussed in this paper. The developed solution is based on FBG sensors measuring the strain profile of the frog of S&C to determine wear size. A numerical model of a 3D prototype was developed through the finite element method, to define loading testing conditions, as well as for comparison with experimental tests. The sensors were examined under periodic and controlled loading tests. Results of this pilot study, based on simulation and laboratory tests, have shown a correlation for the static load. It was shown that the results of the experimental and the numerical studies were in good agreement.


2005 ◽  
Vol 288 (3) ◽  
pp. R591-R599 ◽  
Author(s):  
Mitsuharu Okutsu ◽  
Kenji Ishii ◽  
Kai Jun Niu ◽  
Ryoichi Nagatomi

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1α/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.


2019 ◽  
Vol 21 (2) ◽  
pp. 154-160
Author(s):  
Gianluca Villa ◽  
Rosa Giua ◽  
Timothy Amass ◽  
Lorenzo Tofani ◽  
Cosimo Chelazzi ◽  
...  

Background: In a previous trial, in-line filtration significantly prevented postoperative phlebitis associated with short peripheral venous cannulation. This study aims to describe the cost-effectiveness of in-line filtration in reducing phlebitis and examine patients’ perception of in-hospital vascular access management with and without in-line filtration. Methods: We analysed costs associated with in-line filtration: these data were prospectively recorded during the previous trial. Furthermore, we performed a follow-up for all the 268 patients enrolled in this trial. Among these, 213 patients responded and completed 6 months after hospital discharge questionnaires evaluating the perception of and satisfaction with the management of their vascular access. Results: In-line filtration group required 95.60€ more than the no-filtration group (a mean of € 0.71/patient). In terms of satisfaction with the perioperative management of their short peripheral venous cannulation, 110 (82%) and 103 (76.9%) patients, respectively, for in-line filtration and control group, completed this survey. Within in-line filtration group, 97.3% of patients were satisfied/strongly satisfied; if compared with previous experiences on short peripheral venous cannulation, 11% of them recognised in-line filtration as a relevant causative factor in determining their satisfaction. Among patients within the control group, 93.2% were satisfied/strongly satisfied, although up to 30% of them had experienced postoperative phlebitis. At the qualitative interview, they recognised no difference than previous experiences on short peripheral venous cannulation, and mentioned postoperative phlebitis as a common event that ‘normally occurs’ during a hospital stay. Conclusion: In-line filtration is cost-effective in preventing postoperative phlebitis, and it seems to contribute to increasing patient satisfaction and reducing short peripheral venous cannulation–related discomfort


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rahul Aggarwal ◽  
Nicholas Chiu ◽  
Rishi Wadhera ◽  
Changyu Shen ◽  
Robert W Yeh ◽  
...  

Introduction: Hypertension is a major risk factor for cardiovascular disease. The US government, through the Healthy People Initiative 2020, set targets to improve hypertension prevalence and treatment rates in US adults by a relative 10% from 2005 to 2020, and increase control rates by a relative 40%. We examined US progress towards this goal from 2005-2018. Methods: We analyzed data from 38,876 non-pregnant US adults from the NHANES 2005-2018 surveys to determine nationally representative estimates of hypertension prevalence, treatment rates, and control. Temporal trends in hypertension prevalence, treatment, and control were assessed using weighted linear regression after age adjustment to the 2000 US census (per the Healthy People Initiative approach). In the base case, we defined hypertension as blood pressure >140/90 or on an antihypertensive; we used the ACC/AHA definition of blood pressure >130/80 in sensitivity analyses. Results: In 2017-2018, 34.3% (±1.7) of US adults had hypertension, of these 69.7% (±1.5) were on treatment, and 43.7% (±1.6) were controlled. After age-adjustment, no statistically significant changes in hypertension prevalence, treatment rates, or control were observed from 2005-2018 (p for trend 0.91, ,0.98, 0.66, Figure 1). In sensitivity analyses, applying the ACC/AHA definition increased the estimated prevalence of hypertension during the period, but trends in prevalence remained unchanged. Conclusions: There has been no material progress in reducing the prevalence of hypertension or improving rates of treatment and control from 2005 to 2018. As planning is underway for Healthy People Initiative 2030, setting of hypertension targets must be accompanied with investments in cost-effective, scalable programs to improve blood pressure control nationwide, with a focus on high-risk populations.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Durga M. S. H. Chandrupatla ◽  
Gerrit Jansen ◽  
Elise Mantel ◽  
Philip S. Low ◽  
Takami Matsuyama ◽  
...  

Background. In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptorβ(FRβ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment.Methods. [18F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis. Liver and spleen tissues were stained for ED1/ED2-macrophage markers and FRβexpression.Results. [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p<0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Consistently, ED1- and ED2-positive macrophages were significantly (p<0.01) decreased in liver (4-fold) and spleen (3-fold) of MTX-treated compared with saline-treated rats. Additionally, FRβ-positive macrophages were also significantly reduced in liver (5-fold,p<0.005) and spleen (3-fold,p<0.01) of MTX- versus saline-treated rats.Conclusions. MTX treatment reduced activated macrophages in liver and spleen, as markers for systemic inflammation in these organs. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.


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