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•Provides information about green synthesis of industrial amphiphiles.•Enlists similarity in biosurfactant gene cassettes and biomolecules.•Biosurfactant roles and applications have ...been elucidated.
Microbial surfactants are a large number of amphipathic biomolecules with a myriad of biomolecule constituents from various microbial sources that have been studied for their surface tension reduction activities. With unique properties, their applications have been increased in different areas including environment, medicine, healthcare, agriculture and industries. The present review aims to study the biochemistry and biosynthesis of biosurfactants exhibiting varying biomolecular structures which are produced by different microbial sources. It also provides details on roles played by biosurfactants in nature as well as their potential applications in various sectors. Basic biomolecule content of all the biosurfactants studied showed presence of carbohydrates, aminoacids, lipids and fattyacids. The data presented here would help in designing, synthesis and application of tailor-made novel biosurfactants. This would pave a way for perspectives of research on biosurfactants to overcome the existing bottlenecks in this field.
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Extracellular vesicles (EVs) have garnered significant interest in the biotechnology field due to their intrinsic therapeutic properties as well as their ability to serve as vehicles ...for bioactive cargo. However, the lack of an established biomanufacturing platform and limited potency of EVs in vivo remain critical bottlenecks for clinical translation. In this study, we utilized a 3D-printed scaffold-perfusion bioreactor system to assess the response of dynamic culture on extracellular vesicle production from endothelial cells (ECs). We also investigated whether ethanol conditioning, which was previously shown to enhance vascularization bioactivity of EC-derived EVs produced in standard 2D culture conditions, could be employed successfully for the same purpose in a 3D production system. Our results indicate that dynamic culture in a perfusion bioreactor significantly enhances EV production from human ECs. Moreover, the use of ethanol conditioning in conjunction with dynamic culture induces pro-vascularization bioactivity of EC-derived EVs that is correlated with increased EV levels of pro-angiogenic lncRNAs HOTAIR and MALAT1. Thus, this study represents one of the first reports of rationally-designed EV potency enhancement that is conserved between static 2D and dynamic 3D EV production systems, increasing the potential for scalable biomanufacturing of therapeutic EC-derived EVs for a variety of applications.
Extracellular vesicles (EVs) have substantial therapeutic potential in a variety of applications. However, translation of EV-based therapies may be hindered by biomanufacturing challenges. EV production to date has predominantly involved the use of tissue culture flasks. Here, we report, for the first time, the use of a tubular perfusion bioreactor system with an integrated 3D-printed biomaterial scaffold for EV production from human endothelial cells. This system increases EV yield by over 100-fold compared to conventional tissue culture systems. Further, we show that an ethanol-conditioning approach that our group previously developed in 2D culture for enhancing EV potency is compatible with this new system. Thus, potency enhancement of EVs for vascularization applications is possible even with significantly increased production rate.
Extracellular vesicles (EVs), including exosomes, microvesicles, and others, have emerged as potential therapeutics for a variety of applications. Pre-clinical reports of EV efficacy in treatment of ...non-healing wounds, myocardial infarction, osteoarthritis, traumatic brain injury, spinal cord injury, and many other injuries and diseases demonstrate the versatility of this nascent therapeutic modality. EVs have also been demonstrated to be effective in humans, and clinical trials are underway to further explore their potential. However, for EVs to become a new class of clinical therapeutics, issues related to translation must be addressed. For example, approaches originally developed for cell biomanufacturing, such as hollow fiber bioreactor culture, have been adapted for EV production, but limited knowledge of how the cell culture microenvironment specifically impacts EVs restricts the possibility for rational design and optimization of EV production and potency. In this review, we discuss current knowledge of this issue and delineate potential focus areas for future research towards enabling translation and widespread application of EV-based therapeutics.
•MSC-derived extracellular vesicle therapies require a manufacturing solution.•Process development includes selection of raw materials, platform, and assays.•cGMP-compatibility should be considered ...early in development.
Mesenchymal Stem/Stromal Cells (MSCs) are a well-studied cellular therapy with many clinical trials over the last few decades to treat a range of therapeutic indications. Recently, extracellular vesicles secreted by MSCs (MSC-EVs) have been shown to recapitulate many of the therapeutic effects of the MSCs themselves. While research in MSC-EVs has exploded, it is still early in their development towards a clinical therapy. One of the main challenges in cellular therapy, which will clearly also be a challenge in MSC-EV manufacturing, is developing a scalable, cGMP-compatible manufacturing paradigm. Therefore, the focus of this review is to identify some key MSC-EV manufacturing considerations such as the selection of critical raw materials, manufacturing platforms, and critical quality attribute assays. Addressing these issues early in research and development will accelerate clinical product development, clinical trials, and commercial therapies of MSC-EVs.
PURPOSE OF REVIEWMortality in patients with sarcoidosis has primarily been attributed to advanced pulmonary sarcoidosis. This review aims to provide an update on recent clinical studies that help to ...better phenotype these patients, discuss new treatment options, and suggest areas where additional research is needed.
RECENT FINDINGSDiagnosis and management of advanced pulmonary sarcoidosis has changed as new technologies and treatment options have emerged. Clinical phenotypes of advanced disease have evolved to show overlap in presentation with other interstitial lung diseases. Assessment involves more advanced imaging modalities. New promising treatment options are being studied. Pulmonary rehabilitation and lung transplantation are being utilized to improve health-related quality of life and survival.
SUMMARYPatients with advanced pulmonary fibrosis can have variable clinical, radiographic, histopathologic presentation. Given the poor health-related quality of life and high rates of mortality, medical therapy and pulmonary rehabilitation may benefit these patients. Lung transplantation should be considered in those with end-stage disease.
What Is Hypersensitivity Pneumonitis? Janssen, Brandon; Gomez-Manjarres, Diana; Cosgrove, Gregory ...
American journal of respiratory and critical care medicine,
08/2021, Volume:
204, Issue:
4
Journal Article, Reference
Peer reviewed
Open access
Hypersensitivity pneumonitis (HP) is a lung condition in which your immune system reacts to certain substances in the air you breathe. Repeated inhalation of these substances causes inflammation from ...the lung's immune reaction, called "pneumonitis." Because this inflammation due to HP can resemble pneumonia from an infection, it may take a long time to arrive at the correct diagnosis. Sometimes this inflammation will resolve, but other times, it can lead to scar formation in the lung and problems with absorbing oxygen into your body. Anyone can be affected, but some people are more at risk than others. This fact sheet addresses diagnosis of HP.
A 29-year-old woman who is a never smoker and has a medical history of systemic hypertension presented with a 3-week history of generalized fatigue and dry cough. She endorsed sicca symptoms of dry ...eyes and dry mouth. She denied breathlessness, fever, chills, night sweats, or weight loss. She had no heartburn, postnasal drip, joint pain, swelling, or skin lesions. She had no known lung disease or history of pneumothorax. Her family history was unremarkable.
Pain is an integrated sensory and affective experience. Cortical mechanisms of sensory and affective integration, however, remain poorly defined. Here, we investigate the projection from the primary ...somatosensory cortex (S1), which encodes the sensory pain information, to the anterior cingulate cortex (ACC), a key area for processing pain affect, in freely behaving rats. By using a combination of optogenetics, in vivo electrophysiology, and machine learning analysis, we find that a subset of neurons in the ACC receives S1 inputs, and activation of the S1 axon terminals increases the response to noxious stimuli in ACC neurons. Chronic pain enhances this cortico-cortical connection, as manifested by an increased number of ACC neurons that respond to S1 inputs and the magnified contribution of these neurons to the nociceptive response in the ACC. Furthermore, modulation of this S1→ACC projection regulates aversive responses to pain. Our results thus define a cortical circuit that plays a potentially important role in integrating sensory and affective pain signals.
•Anterior cingulate cortex (ACC) receives inputs from the somatosensory cortex (S1)•Activation of the S1 inputs increases the nociceptive response in the ACC•This cortico-cortical projection regulates pain-aversive behaviors•Chronic pain enhances the connection between the S1 and the ACC
Singh et al. reveal that neurons from the anterior cingulate cortex (ACC) receive inputs from the primary somatosensory cortex (S1) and that the activation of these inputs increases the nociceptive response in the ACC and pain-aversive behaviors. Chronic pain, meanwhile, enhances the nociceptive connection between the S1 and the ACC.
Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as promising drug delivery vehicles for small RNAs (siRNA and miRNA) due to their natural role in intercellular RNA ...transport. However, the application of EVs for therapeutic RNA delivery may be limited by loading approaches that can induce cargo aggregation or degradation. Here, we report the use of sonication as a means to actively load functional small RNAs into EVs. Conditions under which EVs could be loaded with small RNAs with minimal detectable aggregation were identified, and EVs loaded with therapeutic siRNA
via
sonication were observed to be taken up by recipient cells and capable of target mRNA knockdown leading to reduced protein expression. This system was ultimately applied to reduce expression of HER2, an oncogenic receptor tyrosine kinase that critically mediates breast cancer development and progression, and could be extended to other therapeutic targets. These results define important parameters informing the application of sonication as a small RNA loading method for EVs and demonstrate the potential utility of this approach for versatile cancer therapy.
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