scholarly journals Dichloroacetate is an effective treatment for sarcoma models in vitro and in vivo

2014 ◽  
Vol 2 (Suppl 1) ◽  
pp. P9
Author(s):  
Melissa Rooke ◽  
Lucy A Coupland ◽  
Thy Truong ◽  
Anneke C Blackburn
Keyword(s):  
2018 ◽  
Vol 62 (10) ◽  
Author(s):  
James D. Blanchard ◽  
Valerie Elias ◽  
David Cipolla ◽  
Igor Gonda ◽  
Luiz E. Bermudez

ABSTRACT Nontuberculous mycobacteria (NTM) affect an increasing number of individuals worldwide. Infection with these organisms is more common in patients with chronic lung conditions, and treatment is challenging. Quinolones, such as ciprofloxacin, have been used to treat patients, but the results have not been encouraging. In this report, we evaluate novel formulations of liposome-encapsulated ciprofloxacin (liposomal ciprofloxacin) in vitro and in vivo. Its efficacy against Mycobacterium avium and Mycobacterium abscessus was examined in macrophages, in biofilms, and in vivo using intranasal instillation mouse models. Liposomal ciprofloxacin was significantly more active than free ciprofloxacin against both pathogens in macrophages and biofilms. When evaluated in vivo, treatment with the liposomal ciprofloxacin formulations was associated with significant decreases in the bacterial loads in the lungs of animals infected with M. avium and M. abscessus. In summary, topical delivery of liposomal ciprofloxacin in the lung at concentrations greater than those achieved in the serum can be effective in the treatment of NTM, and further evaluation is warranted.


Processes ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 937 ◽  
Author(s):  
Dongdong Wang ◽  
Jiansheng Huang ◽  
Andy Wai Kan Yeung ◽  
Nikolay T. Tzvetkov ◽  
Jarosław O. Horbańczuk ◽  
...  

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there have been more than 10 million reported cases, more than 517,000 deaths in 215 countries, areas or territories. There is no effective antiviral medicine to prevent or treat COVID-19. Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. There is increasing number of publications reporting the effect of natural products and traditional medicine products on COVID-19. In our review, we provide an overview of natural products and their derivatives or mimics, as well as traditional medicine products, which were reported to exhibit potential to inhibit SARS-CoV-2 infection in vitro, and to manage COVID-19 in vivo, or in clinical reports or trials. These natural products and traditional medicine products are categorized in several classes: (1) anti-malaria drugs including chloroquine and hydroxychloroquine, (2) antivirals including nucleoside analogs (remdesivir, favipiravir, β-D-N4-hydroxycytidine, ribavirin and among others), lopinavir/ritonavir and arbidol, (3) antibiotics including azithromycin, ivermectin and teicoplanin, (4) anti-protozoal drug, emetine, anti-cancer drug, homoharringtonine, and others, as well as (5) traditional medicine (Lian Hua Qing Wen Capsule, Shuang Huang Lian Oral Liquid, Qingfei Paidu Decoction and Scutellariae Radix). Randomized, double-blind and placebo-controlled large clinical trials are needed to provide solid evidence for the potential effective treatment. Currently, drug repurposing is a promising strategy to quickly find an effective treatment for COVID-19. In addition, carefully combined cocktails need to be examined for preventing a COVID-19 pandemic and the resulting global health concerns.


Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 165
Author(s):  
Rongfeng Li ◽  
Huahua Yu ◽  
Aoyu Li ◽  
Chunlin Yu ◽  
Pengcheng Li

Jellyfish stings are a common issue globally, particularly in coastal areas in the summer. Victims can suffer pain, itching, swelling, shock, and even death. Usually, hot water, vinegar, or alumen is used to treat the normal symptoms of a jellyfish sting. However, a specific antivenom may be an effective treatment to deal with severe jellyfish stings. Cyanea nozakii often reach a diameter of 60 cm and are responsible for hundreds of thousands of stings per year in coastal Chinese waters. However, there has been no specific C. nozakii antivenom until now, and so the development of this antivenom is very important. Herein, we collected C. nozakii antisera from tentacle extract venom immunized rabbits and purified the immunoglobulin (IgG) fraction antivenom (AntiCnTXs). Subsequently, two complete procedures to produce a refined F(ab’)2 type of antivenom (F(ab’)2-AntiCnTXs) and Fab type of antivenom (Fab-AntiCnTXs) by multiple optimizations and purification were established. The neutralization efficacy of these three types of antivenoms was compared and analyzed in vitro and in vivo, and the results showed that all types of antibodies displayed some neutralization effect on the lethality of C. nozakii venom toxins, with the neutralization efficacy as follows: F(ab’)2-AntiCnTXs ≥ AntiCnTXs > Fab-AntiCnTXs. This study describes the preparation of novel C. nozakii jellyfish antivenom preparations towards the goal of developing a new, effective treatment for jellyfish stings.


2020 ◽  
Vol 186 ◽  
pp. 110681 ◽  
Author(s):  
Sonia S. Pandey ◽  
Furqan A. Maulvi ◽  
Priya S. Patel ◽  
Manish R. Shukla ◽  
Kinjal M. Shah ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Amol Shindikar ◽  
Akshita Singh ◽  
Malcolm Nobre ◽  
Saurabh Kirolikar

Researchers have made considerable progress in last few decades in understanding mechanisms underlying pathogenesis of breast cancer, its phenotypes, its molecular and genetic changes, its physiology, and its prognosis. This has allowed us to identify specific targets and design appropriate chemical entities for effective treatment of most breast cancer phenotypes, resulting in increased patient survivability. Unfortunately, these strategies have been largely ineffective in the treatment of triple negative breast cancer (TNBC). Hormonal receptors lacking render the conventional breast cancer drugs redundant, forcing scientists to identify novel targets for treatment of TNBC. Two natural compounds, curcumin and resveratrol, have been widely reported to have anticancer properties.In vitroandin vivostudies show promising results, though their effectiveness in clinical settings has been less than satisfactory, owing to their feeble pharmacokinetics. Here we discuss these naturally occurring compounds, their mechanism as anticancer agents, their shortcomings in translational research, and possible methodology to improve their pharmacokinetics/pharmacodynamics with advanced drug delivery systems.


2017 ◽  
Author(s):  
Tai-Di Chen ◽  
Jeong-Hun Ko ◽  
Maria Prendecki ◽  
Stephen P. McAdoo ◽  
Charles D. Pusey ◽  
...  

AbstractCrescentic glomerulonephritis represents the most severe form of antibody-mediated glomerulonephritis. It is an important cause of renal dysfunction worldwide and there is a need for more effective treatment. Deferiprone, an orally active iron chelator, is widely used in patients with thalassemia. Here we present the preventive and therapeutic effects of deferiprone in experimental crescentic glomerulonephritis. Nephrotoxic nephritis was induced in Wistar Kyoto rats, and preventive treatment with deferiprone substantially lowered glomerular crescent formation by 84%, with 70% reduction in proteinuria. In established glomerulonephritis, deferiprone treatment effectively halted glomerular inflammation, reversed progression of proteinuria, and prevented deterioration of renal function. Deferiprone reduced glomerular inflammatory cell proliferation in vivo. It was internalised by monocyte/macrophages and inhibited their proliferation in vitro, without showing cellular toxicity. Interestingly, deferiprone showed a neutralizing effect on superoxide anions, and prevented the expression of monocyte chemoattractant protein-1 and matrix metalloproteinase 9, 12 and 14, by primary macrophages. These results suggest that deferiprone partly exerts its renal protective effect through inhibition of monocyte/macrophage proliferation and function by iron-chelating and anti-oxidant properties, respectively. We conclude that deferiprone is an effective treatment in a severe and reproducible model of antibody-mediated glomerular inflammation that resembles human crescentic glomerulonephritis, indicating its therapeutic potential.


2020 ◽  
Author(s):  
Daoyong Li ◽  
Chao Wu ◽  
He Tian ◽  
Liang Mao ◽  
Zhanshan Gao ◽  
...  

Abstract Background:Impaired wound healing is one of the important complications of diabetes. However, the specific pathogenesis is still unclear, and there is no effective treatment. Macrophages pretreated with chemical or biological factors may increase the biological activity of macrophage-derived exosomes, which is expected to become a new effective treatment method. The purpose of this study was to investigate whether the exosomes secreted by macrophages pretreated with lipopolysaccharide (LPS) have better anti-inflammatory and angiogenic abilities in the treatment of diabetic wound healing and their underlying molecular mechanisms.Methods:In this study, macroscopical, biochemical, histological, immunofluorescence and molecular biology methods were used to evaluate the potential protective mechanism and effect of lipopolysaccharide stimulated macrophage exosomes (LPS-Exos) on wound healing in streptozotocin induced hyperglycemia rats.In the in vivo experiment, the percentages of wound closure and contraction were compared and analyzed on the 7th, 14th, and 21st day after treatment by grouping treatments with different concentrations of LPS-Exos.At the same time, hematoxylin and eosin staining (HE), Masson staining, immunofluorescence staining and Western blotting (WB) were used for histological analysis of the wound tissue on the 14th day after injury to evaluate the impact of different treatment methods on wound healing.In in vitro experiments, the ability of endothelial cells related to proliferation, migration, tube formation and the expression of vascular endothelial growth factor (VEGF) were tested.At the same time, in vivo and in vitro experiments, the effect of Nrf2/HO-1 signaling pathway on LPS-Exos in inhibiting inflammation and promoting angiogenesis was evaluated by using exosome-specific inhibitors.Results:LPS-Exos reduced the content of ROS and MDA in the wound tissue of hyperglycemic rats, increased the activity of SOD and the production of GSH-Px, activated the Nrf2/HO-1 pathway, inhibited the expression of inflammation-related proteins, and promoted blood vessels generate. The group given exosome inhibitors reversed this phenomenon.Conclusions: LPS-Exos may activate the Nrf2/HO-1 defense pathway, improve endothelial cell function, inhibit oxidative damage and inflammation, and promote wound healing in diabetic rats, thereby having the potential to treat diabetic skin defects.


2020 ◽  
Vol 11 (4) ◽  
pp. 11172-11186

The challenges of SARS-CoV-2 have frightened the world due to a lack of effective treatment. Many clinicians have adopted drug repositioning because of the urgent need to contain the viral pandemic. Several studies have demonstrated the in vitro and in vivo antiviral efficacy of chloroquine and hydroxychloroquine in the treatment of SARS-CoV-2. However, the cardiovascular toxicity of chloroquine and hydroxychloroquine stand as a limitation to their general use to treat SARS-CoV-2. Thus, it is necessitated the search for an adjuvant that could be used alongside these treatments to mitigate the undesired effect. The cardioprotective activity of resveratrol could serve to mitigate the cardiovascular toxicity of chloroquine and hydroxychloroquine. Its antioxidant and anti-inflammatory properties synergistically with chloroquine or hydroxychloroquine could also mitigate the antiviral activity of SARS-CoV-2. In this review, we explore chloroquine and hydroxychloroquine for SARS-CoV-2 treatment and suggest their synergetic use with resveratrol as a recommended therapy to mitigate cardiovascular toxicity and contribute to their antiviral effects.


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