scholarly journals Thrombus-Targeting Polymeric Nanocarriers and Their Biomedical Applications in Thrombolytic Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Qixiao Guan ◽  
Hongjing Dou

Due to the high morbidity and mortality of cardiovascular diseases, there is an urgent need for research on antithrombotic strategies. In view of the short half-life, insufficient drug penetration, poor targeting capabilities, and hemorrhagic side-effects of traditional thrombus treatment methods, the combination of thrombolytic therapy and nanocarriers brought by the development of nanotechnology in recent years may provide effective solutions for these undesirable side-effects caused by insufficient targeting. Polymeric nanocarriers, based on macromolecules and various functional groups, can connect specific targeting molecules together through chemical modification to achieve the protection and targeted delivery of thrombolytic drugs. However, simple chemical molecular modifications may be easily affected by the physiological environment encountered in the circulatory system. Therefore, the modification of nanocarriers with cell membranes can provide camouflage to these platforms and help to extend their circulation time while also imparting them with the biological functions of cell membranes, thus providing them with precise targeting capabilities, among which the most important is the biological modification of platelet membranes. In addition, some nanoparticles with their own therapeutic functions have also been developed, such as polypyrrole, which can exhibit a photothermal effect to induce thrombolysis. Herein, combined with the mechanism of thrombosis and thrombolysis, we outline the recent advances achieved with thrombus-targeting nanocarriers with regard to thrombosis treatment. On this basis, the design considerations, advantages, and challenges of these thrombolytic therapies in clinical transformation are discussed.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1110.1-1111
Author(s):  
J. Qiao ◽  
S. X. Zhang ◽  
T. T. Zhang ◽  
J. Zhang ◽  
M. T. Qiu ◽  
...  

Background:Systemic sclerosis (scleroderma, SSc) is a rare complex connective tissue disease associated with high mortality and high morbidity1. Active SSc are typically treated with immunosuppressants, which may create a variety of severe side-effects, especially for long-term treatment2. As the pathogenesis of SSc is still a matter of debate, growing evidences have focused on the immune disorders3. However, the quantitative status of lymphocyte subsets in SSc patients are unclear and effects of immunomodulatory combination therapies (avoiding side-effects of conventional therapy) on the lymphocyte subsets are unknown.Objectives:To investigate the quantitative status of peripheral lymphocyte subpopulations and CD4+T subsets in SSc patients for the exploration of SSc pathogenesis and evaluate the effects of new immunomodulatory combination therapies on those cells.Methods:From July 2014 to December 2019, total 166 patients with SSc and 206 healthy controls (HCs) were enrolled in this study, in which, 79 follow-up patients received immunomodulatory drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid and coenzyme Q10. The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and Tregs in peripheral blood of these subjects were detected by flow cytometry combined with standard absolute counting beads.Results:Patients with SSc had lower absolute counts of total T, NK, Th2, Th17 and Tregs as compared with those of HCs (P<0.05) (Figure 1). After immunomodulatory combination treatments, there were increases in a various of peripheral lymphocyte subsets such as T, B and CD8+T (P< 0.05). Moreover, the increased level of Tregs was much more dramatical than those of other lymphocyte subsets, resulting in the decrease ratios of Teffs/Tregs such as Th1/Tregs and Th2/Tregs and rebuilding immunologic equilibrium (Figure 2).Conclusion:This cross-sectional study clarified the abnormal status of lymphocyte subsets in SSc patients, suggesting lymphocyte subsets, especially Tregs, might be relevant and play a crucial role in the pathogenesis of SSc, thus providing a potential therapeutic target for SSc patients. Immunomodulatory combination therapies effectively increase the level of Tregs as well as other lymphocytes to some degree and maintain the immunologic equilibrium, which may help for SSc patients’ symptom remission.References:[1]Denton CP, Khanna D. Systemic sclerosis. Lancet 2017;390(10103):1685-99. doi: 10.1016/S0140-6736(17)30933-9 [published Online First: 2017/04/18][2]Winthrop KL, Weinblatt ME, Bathon J, et al. Unmet need in rheumatology: reports from the Targeted Therapies meeting 2019. Ann Rheum Dis 2020;79(1):88-93. doi: 10.1136/annrheumdis-2019-216151 [published Online First: 2019/10/31][3]Skaug B, Khanna D, Swindell WR, et al. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Ann Rheum Dis 2019 doi: 10.1136/annrheumdis-2019-215894 [published Online First: 2019/11/27]Acknowledgments :None.Disclosure of Interests:None declared


2021 ◽  
Vol 66 (3) ◽  
pp. 9-12
Author(s):  
A. Lyaginskaya ◽  
N. Shandala ◽  
E. Metlyaev ◽  
V. Kuptsov ◽  
O. Parinov

Purpose: To identify the problem of assessing the health status of personnel working under the conditions of new technologies for the production of nuclear fuel. Material and method: The object of the research was the general morbidity of workers in the production of mixed nitride uranium-plutonium fuel (MNUP-fuel). The material for the study was the data presented in the «Health Passports». The paper used the method of comparative analysis of the overall morbidity of workers in the production of MNUP-fuel and workers in enterprises dealing with nuclear fuel. Results and analysis: At present, in our country, within the framework of the «Breakthrough» project, new technologies are being developed for the fabrication and refurbishment of mixed uranium-plutonium (MNUP) fuel. In the absence of radiation and hygienic standards for the content of fuel products in working rooms, in order to assess the influence of production factors, along with the radiation dose, the incidence of personnel is studied as an integral indicator of health. A study of the incidence of 50 workers in the production of MNUP fuel revealed: Relatively high incidence of general morbidity – 1122 diseases per 100 people or an average of 93.5 diseases per 100 people per year, regardless of the length of service. The leading diseases in the overall morbidity structure are diseases of the respiratory system – 26.0 % (1st place), eyes – 13.4 % (2nd place), musculoskeletal system – 11.4 % (3rd place), circulatory system – 10,9 % (4th place), injuries and poisoning – 8.4 % (5th place), digestive organs and genitourinary system – 7.7 % and 7.0 %, respectively (6th place), which make up 84.7 % of the total morbidity. Obviously, the effective dose of 4.6 mSv/year cannot be the only reason for the high morbidity in workers in complex radiochemical production, but characterizes only the influence of one of the many nonspecific factors of production. The existing system for assessing the health of personnel working in radiochemical production, in addition to analyzing the risks of deterministic and stochastic effects, should include an assessment of the overall morbidity of personnel.


2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Joshua Billy Hannabuss

<strong>PICO question</strong><br /><p>Of cats that present with aortic thromboembolism, do patients that receive thrombolytic therapy in the acute phase have improved survival as compared to those who do not?</p><strong>Clinical bottom line</strong><br /><p>Based on the current available evidence, the use of thrombolytic therapy in the acute phase of aortic thromboembolism (ATE) does not appear to improve survival when compared to conventional supportive therapy. Frequently reported adverse side effects further questions its merits, and large scale controlled clinical trials would be required to further evaluate any benefit in the use of this therapy.</p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/pr-icon.jpg" alt="Peer Reviewed" />


2018 ◽  
Vol 58 (6) ◽  
pp. 324-327
Author(s):  
Daisuke TADAKI ◽  
Daichi YAMAURA ◽  
Xingyao FENG ◽  
Ayumi HIRANO-IWATA

2020 ◽  
Vol 16 (11) ◽  
pp. 942-948
Author(s):  
Rahila Qureshi ◽  

Leishmaniasis is one of the most neglected diseases with high morbidity and mortality rate. Severe side effects with existing drug and lack of proper vaccine encouraged us to design alternative models to combat the disease. We showed that PP1 of Leishmania donovani mediates immunomodulation in host macrophages needed for parasite survival. Therefore, it is of interest to report the molecular docking analysis of 512 isoflavone derivatives with the phosphatase 1 protein from Leishmania donovani to highlight compound 362 (5-hydroxy-5-{9-[2-methoxy-2-(2-methylfuran-3-yl) ethyl]-1H,3H,4H,10bH-pyrano[4,3-c]chromen-3-yl}pentanoic acid) having good binding features and acceptable ADMET properties for further consideration.


2021 ◽  
Vol 5 (1) ◽  
pp. 1234-1238
Author(s):  
N. Pabivantsava ◽  

In order to substantiate organizational measures for early detection and tertiary prevention of cardiovascular diseases, the causal relationships of high morbidity, disability, and mortality due to cardiovascular diseases, coronary heart disease and its complications were studied in the population of the Brest region in the period from 2006 to 2010. Measures to improve the organization of preventive medical examination of patients from cardiovascular risk groups with prognostically unfavorable outcomes were suggested. Through the implementation of an organizational experiment in 2012-2017, it was possible to achieve a positive medical and social effect, expressed in increasing the availability of multi-level and high-tech care to patients in need, as well as in improving the medical and demographic indicators of the Brest region in general and in the diseases of the circulatory system in particular, which formed the basis of the second part of this article.


Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 486 ◽  
Author(s):  
Santosh Kumar ◽  
Kaining Zhi ◽  
Ahona Mukherji ◽  
Kelli Gerth

In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of 15 April 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.


Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 120 ◽  
Author(s):  
Bakhtiar Bukari ◽  
Rasika M. Samarasinghe ◽  
Jinjutha Noibanchong ◽  
Sarah L. Shigdar

The blood-brain barrier (BBB) is a highly specialised network of blood vessels that effectively separates the brain environment from the circulatory system. While there are benefits, in terms of keeping pathogens from entering the brain, the BBB also complicates treatments of brain pathologies by preventing efficient delivery of macromolecular drugs to diseased brain tissue. Although current non-invasive strategies of therapeutics delivery into the brain, such as focused ultrasound and nanoparticle-mediated delivery have shown various levels of successes, they still come with risks and limitations. This review discusses the current approaches of therapeutic delivery into the brain, with a specific focus on non-invasive methods. It also discusses the potential for aptamers as alternative delivery systems and several reported aptamers with promising preliminary results.


2019 ◽  
Vol 78 ◽  
pp. 01009
Author(s):  
Yanan Yin ◽  
Weiwei Yang ◽  
Yingliang Jiao ◽  
He Yang ◽  
Xinglin Li

Diabetes is an endocrine system disease characterized by high morbidity, high prevalence, and high mortality. Although the traditional medicine for treating diabetes has a good effect, its side effects are also large. Traditional Chinese medicine has also achieved good therapeutic effects in the treatment of diabetes, and the side effects of Chinese medicine are small. Coix is a medicinal and edible plant. It is used as food and medicine alone or in combination with other herbs in the early days. Its seeds have become one of the most popular Chinese herbal medicines. The coixan was extracted from Coix seed, and it was administered to diabetic mice. After five weeks of treatment, it was found to have some role in hypoglycemic. This study provides a good application prospect for Chinese medicine treatment of diabetes.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1189
Author(s):  
Vijay Sagar Madamsetty ◽  
Krishnendu Pal ◽  
Shamit Kumar Dutta ◽  
Enfeng Wang ◽  
Debabrata Mukhopadhyay

Despite recent advancements, effective treatment for pancreatic ductal adenocarcinoma (PDAC) has remained elusive. The overall survival rate in PDAC patients has been dismally low due to resistance to standard therapies. In fact, the failure of monotherapies to provide long-term survival benefits in patients led to ascension of several combination therapies for PDAC treatment. However, these combination therapies provided modest survival improvements while increasing treatment-related adverse side effects. Hence, recent developments in drug delivery methods hold the potential for enhancing therapeutic benefits by offering cocktail drug loading and minimizing chemotherapy-associated side effects. Nanoformulations-aided deliveries of anticancer agents have been a success in recent years. Yet, improving the tumor-targeted delivery of drugs to PDAC remains a major hurdle. In the present paper, we developed several new tumor-targeted dual intervention-oriented drug-encapsulated (DIODE) liposomes. We successfully formulated liposomes loaded with gemcitabine (G), paclitaxel (P), erlotinib (E), XL-184 (c-Met inhibitor, X), and their combinations (GP, GE, and GX) and evaluated their in vitro and in vivo efficacies. Our novel DIODE liposomal formulations improved median survival in comparison with gemcitabine-loaded liposomes or vehicle. Our findings are suggestive of the importance of the targeted delivery for combination therapies in improving pancreatic cancer treatment.


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