scholarly journals Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
C. H. Masterson ◽  
A. Ceccato ◽  
A. Artigas ◽  
C. dos Santos ◽  
P. R. Rocco ◽  
...  
Keyword(s):  
Lung Injury ◽  
Clinical Studies ◽  
Therapeutic Potential ◽  
Viral Pneumonia ◽  
Therapeutic Approaches ◽  
Translation Strategies ◽  
Challenges And Opportunities ◽  
Multiple Trials ◽  
Stromal Stem Cells

AbstractSevere viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to ‘licence’ or ‘pre-activate’ these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.

Therapeutic Potential of Mesenchymal Stromal Stem Cells in Rheumatoid Arthritis: a Systematic Review of In Vivo Studies

2020 ◽  
Vol 16 (2) ◽  
pp. 276-287 ◽  
Author(s):  
Alexia Karamini ◽  
Athina Bakopoulou ◽  
Dimitrios Andreadis ◽  
Konstantinos Gkiouras ◽  
Aristeidis Kritis
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Stem Cells ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Stromal Stem Cells

Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates lung injury during mechanical ventilation

2019 ◽  
Author(s):  
Christopher Bobba ◽  
Qinqin Fei ◽  
Vasudha Shukla ◽  
Hyunwook Lee ◽  
Pragi Patel ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Therapeutic Potential ◽  
Compensatory Response ◽  
Nanoparticle Delivery ◽  
Biophysical Forces ◽  
Delivery Platform ◽  
In Vitro Systems

ABSTRACTDuring mechanical ventilation, injurious biophysical forces exacerbate lung injury. These forces disrupt alveolar capillary barrier integrity, trigger proinflammatory mediator release, and differentially regulate genes and non-coding oligonucleotides such as microRNAs. In this study, we identify miR-146a as a mechanosensitive microRNA in alveolar macrophages that has therapeutic potential to mitigate lung injury during mechanical ventilation. We used humanized in-vitro systems, mouse models, and biospecimens from mechanically ventilated patients to elucidate the expression dynamics of miR-146a that might be required to decrease lung injury during mechanical ventilation. We found that the endogenous increase in miR-146a following injurious was relatively modest and not sufficient to prevent lung injury. However, when miR-146a was highly overexpressed using a nanoparticle-based delivery platform in vivo, it was sufficient to prevent lung injury. These data indicate that the endogenous increase in microRNA-146a during MV is a compensatory response that only partially limits VILI and that nanoparticle delivery approaches that significantly over-express microRNA-146a in AMs is an effective strategy for mitigating VILI.

scholarly journals Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seongchan Kim ◽  
Shin Young Kim ◽  
Seung Joon Rho ◽  
Seung Hoon Kim ◽  
So Hyang Song ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Intratracheal Instillation ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

scholarly journals Cannabis sativa and Skin Health: Dissecting the Role of Phytocannabinoids

Planta Medica ◽  
2021 ◽  
Author(s):  
Giulia Martinelli ◽  
Andrea Magnavacca ◽  
Marco Fumagalli ◽  
Mario DellʼAgli ◽  
Stefano Piazza ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Skin Diseases ◽  
Cannabis Sativa ◽  
Therapeutic Potential ◽  
Current Evidence ◽  
Skin Disorders ◽  
Anti Inflammatory

AbstractThe use of Cannabis sativa is currently recognized to ease certain types of chronic pain, reduce chemotherapy-induced nausea, and improve anxiety. Nevertheless, few studies highlighted the therapeutic potential of C. sativa extracts and related phytocannabinoids for a variety of widespread skin disorders including acne, atopic dermatitis, psoriasis, pruritus, and pain. This review summarized the current evidence on the effects of phytocannabinoids at the cutaneous level through the collection of in vitro, in vivo, and clinical studies published on PubMed, Scopus, Embase, and Web of Science until October 2020. Phytocannabinoids have demonstrated potential anti-inflammatory, antioxidant, anti-aging, and anti-acne properties by various mechanisms involving either CB1/2-dependent and independent pathways. Not only classical immune cells, but also several skin-specific actors, such as keratinocytes, fibroblasts, melanocytes, and sebocytes, may represent a target for phytocannabinoids. Cannabidiol, the most investigated compound, revealed photoprotective, antioxidant, and anti-inflammatory mechanisms at the cutaneous level, while the possible impact on cell differentiation, especially in the case of psoriasis, would require further investigation. Animal models and pilot clinical studies supported the application of cannabidiol in inflammatory-based skin diseases. Also, one of the most promising applications of non-psychotropic phytocannabinoids is the treatment of seborrheic disorders, especially acne. In conclusion, the incomplete knowledge of the role of the endocannabinoid system in skin disorders emerged as an important limit for pharmacological investigations. Moreover, the limited studies conducted on C. sativa extracts suggested a higher potency than single phytocannabinoids, thus stimulating new research on phytocannabinoid interaction.

scholarly journals Current Regulatory Requirements for Biosimilars in Six Member Countries of BRICS-TM: Challenges and Opportunities

2021 ◽  
Vol 8 ◽  
Author(s):  
Hasumati Rahalkar ◽  
Alan Sheppard ◽  
Gustavo Mendes Lima Santos ◽  
Chitralekha Dasgupta ◽  
Sonia Mayra Perez-Tapia ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Marketing Authorisation ◽  
Analytical Data ◽  
Cost Effective ◽  
Regulatory Agencies ◽  
Regulatory Requirements ◽  
Confidential Data ◽  
Data Assessment ◽  
Challenges And Opportunities

Background: The aim of the study was to identify, interpret, and compare the current perspectives of regulatory agencies in six member countries of BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, and Mexico) on the different criteria used for biosimilar development and marketing authorisation process.Methods: A semi-quantitative questionnaire was developed covering the organisation of agency, biosimilar development criteria and marketing authorisation process and sent to seven regulatory agencies covering the BRICS-TM countries. All data was kept anonymous and confidential. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data.Results: Out of the seven regulatory agencies included in the study, six representatives provided the responses. The perspectives of these six regulatory agencies varied on a number of aspects relating to the review criteria for biosimilar development and licencing process. The most prevalent model for data assessment is the “full review” of a marketing authorisation application. There is lack of a standard approach across the agencies on sourcing of the reference biological product, in vivo toxicity studies and confirmatory clinical studies. Most agencies restrict interaction with biosimilar developers and any scientific advice is non-binding. The marketing authorisation approval depends on scientific assessment of the dossier, sample analysis and GMP certification. The agencies do not issue any public assessment report specifying the summary basis of biosimilar approval.Conclusion: Regulatory agencies across the six emerging economies are steadily improving the regulatory mechanism in the area of biosimilars. However, there remains scope for increasing the effectiveness and efficiency of the processes by encouraging open and transparent interaction with developers, adopting a flexible approach toward accepting advanced analytical data in lieu of clinical studies and enhancing regulatory reliance amongst agencies. This will help to simplify the new biosimilar development programmes and make them more cost-effective.

scholarly journals Corylin Ameliorates LPS-Induced Acute Lung Injury via Suppressing the MAPKs and IL-6/STAT3 Signaling Pathways

2021 ◽  
Vol 14 (10) ◽  
pp. 1046
Author(s):  
I-Chen Chen ◽  
Shu-Chi Wang ◽  
Yi-Ting Chen ◽  
Hsin-Han Tseng ◽  
Po-Len Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Lavage Fluid ◽  
Mitogen Activated Protein ◽  
Associated Proteins ◽  
Anti Inflammatory

Acute lung injury (ALI) is a high mortality disease with acute inflammation. Corylin is a compound isolated from the whole plant of Psoralea corylifolia L. and has been reported to have anti-inflammatory activities. Herein, we investigated the therapeutic potential of corylin on lipopolysaccharides (LPS)-induced ALI, both in vitro and in vivo. The levels of proinflammatory cytokine secretions were analyzed by ELISA; the expressions of inflammation-associated proteins were detected using Western blot; and the number of immune cell infiltrations in the bronchial alveolar lavage fluid (BALF) were detected by multicolor flow cytometry and lung tissues by hematoxylin and eosin (HE) staining, respectively. Experimental results indicated that corylin attenuated LPS-induced IL-6 production in human bronchial epithelial cells (HBEC3-KT cells). In intratracheal LPS-induced ALI mice, corylin attenuated tissue damage, suppressed inflammatory cell infiltration, and decreased IL-6 and TNF-α secretions in the BALF and serum. Moreover, it further inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including p-JNK, p-ERK, p-p38, and repressed the activation of signal transducer and activator of transcription 3 (STAT3) in lungs. Collectively, our results are the first to demonstrate the anti-inflammatory effects of corylin on LPS-induced ALI and suggest corylin has significant potential as a novel therapeutic agent for ALI.

scholarly journals Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

2021 ◽  
Vol 22 (20) ◽  
pp. 11069
Author(s):  
Ridhima Kaul ◽  
Pradipta Paul ◽  
Sanjay Kumar ◽  
Dietrich Büsselberg ◽  
Vivek Dhar Dwivedi ◽  
...  
Keyword(s):  
Therapeutic Intervention ◽  
Clinical Studies ◽  
In Silico ◽  
Therapeutic Potential ◽  
Health Concern ◽  
N Protein ◽  
Synthetic Drugs ◽  
In Silico Studies

The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches

2019 ◽  
Vol 26 (5) ◽  
pp. 765-779 ◽  
Author(s):  
Alexios S. Antonopoulos ◽  
Athina Goliopoulou ◽  
Evangelos Oikonomou ◽  
Sotiris Tsalamandris ◽  
Georgios-Angelos Papamikroulis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Studies ◽  
Redox State ◽  
Redox Balance ◽  
Therapeutic Approaches ◽  
Critical Determinant ◽  
Electrophysiological Properties ◽  
Antioxidant Agents ◽  
Clinical Benefits

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

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