The translation potential of harnessing the resolution of inflammation.
Ontology highlight
ABSTRACT:
SUBMITTER: Collins G
PROVIDER: S-EPMC10292660 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
The translation potential of harnessing the resolution of inflammation.
Collins George G de Souza Carvalho Jhonatan J Gilroy Derek W DW
The Journal of allergy and clinical immunology 20230621 2
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Project description:Several chronic inflammatory diseases are associated with non-resolving inflammation. Conventional anti-inflammatory drugs fail to completely cure these diseases. Resolution pharmacology is a new therapeutic approach based on the use of pro-resolving mediators that accelerate the resolution phase of inflammation by targeting the productive phase of inflammation. Indeed, pro-resolving mediators prevent leukocyte recruitment and induce apoptosis of accumulated leukocytes. This approach is now called resolution therapy with the introduction of complex biological drugs and cell-based therapies. The main objective of resolution therapy is to specifically reduce the duration of the resolution phase to accelerate the return to homeostasis. Under physiological conditions, macrophages play a critical role in the resolution of inflammation. Indeed, after the removal of apoptotic cells (a process called efferocytosis), macrophages display anti-inflammatory reprogramming and subsequently secrete multiple pro-resolving factors. These factors can be used as resolution therapy. Here, we review the different mechanisms leading to anti-inflammatory reprogramming of macrophages after efferocytosis and the pro-resolving factors released by these efferocytic macrophages. We classify these mechanisms in three different categories: macrophage reprogramming induced by apoptotic cell-derived factors, by molecules expressed by apoptotic cells (i.e., "eat-me" signals), and induced by the digestion of apoptotic cell-derived materials. We also evoke that macrophage reprogramming may result from cooperative mechanisms, for instance, implicating the apoptotic cell-induced microenvironment (including cellular metabolites, specific cytokines or immune cells). Then, we describe a new drug candidate belonging to this resolution therapy. This candidate, called SuperMApo, corresponds to the secretome of efferocytic macrophages. We discuss its production, the pro-resolving factors present in this drug, as well as the results obtained in experimental models of chronic (e.g., arthritis, colitis) and acute (e.g., peritonitis or xenogeneic graft-versus-host disease) inflammatory diseases.
| S-EPMC9651061 | biostudies-literature
Project description:Reducing inflammation by diet is a major goal for prevention or lowering symptoms of a variety of diseases, such as auto-immune reactions and cancers. Natural polysaccharides are increasingly gaining attention due to their potential immunomodulating capacity. Structures of those molecules are highly important for their effects on the innate immune system, cytokine production and secretion, and enzymes in immune cells. Such polysaccharides include β-glucans, pectins, fucoidans, and fructans. To better understand the potential of these immunomodulatory molecules, it is crucial to enhance dedicated research in the area. A bibliometric analysis was performed to set a starting observation point. Major pillars of inflammation, such as pattern recognition receptors (PRRs), enzymatic production of inflammatory molecules, and involvement in specific pathways such as Nuclear-factor kappa-B (NF-kB), involved in cell transcription, survival, and cytokine production, and mitogen-activated protein kinase (MAPK), a regulator of genetic expression, mitosis, and cell differentiation. Therefore, the outcomes from polysaccharide applications in those scenarios are discussed.
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Project description:Directed evolution of a cyanobacterial phytochrome was undertaken to elucidate the structural basis of its light sensory activity by remodeling the chemical environment of its linear tetrapyrrole prosthetic group. In addition to identifying a small region of the apoprotein critical for maintaining phytochrome's native spectroscopic properties, our studies revealed a tyrosine-to-histidine mutation that transformed phytochrome into an intensely red fluorescent biliprotein. This tyrosine is conserved in all members of the phytochrome superfamily, implicating direct participation in the primary photoprocess of phytochromes. Fluorescent phytochrome mutants also hold great promise to expand the present repertoire of genetically encoded fluorescent proteins into the near infrared.
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Project description:The concept behind the resolution of inflammation has changed in the past decades from a passive to an active process, which reflects in novel avenues to understand and control inflammation-driven diseases. The time-dependent and active process of resolution phase is orchestrated by the endogenous biosynthesis of specialized pro-resolving lipid mediators (SPMs). Inflammation and its resolution are two forces in rheumatic diseases that affect millions of people worldwide with pain as the most common experienced symptom. The pathophysiological role of SPMs in arthritis has been demonstrated in pre-clinical and clinical studies (no clinical trials yet), which highlight their active orchestration of disease control. The endogenous roles of SPMs also give rise to the opportunity of envisaging these molecules as novel candidates to improve the life quality of rhematic diseases patients. Herein, we discuss the current understanding of SPMs endogenous roles in arthritis as pro-resolutive, protective, and immunoresolvent lipids.
| S-EPMC8440959 | biostudies-literature
Project description: Not available
| S-EPMC11912138 | biostudies-literature
Project description:The intrinsic connection between inflammation and tumor promotion is well characterized and is a key pathogenic event in patients with colorectal cancer (CRC), the second most common cause of tumor-related death in western countries. Environmental factors and chronic inflammation represent the major causes of intestinal carcinogenesis. In fact, patients suffering from inflammatory bowel diseases, including Crohn’s disease and Ulcerative Colitis (UC), have high risk of developing colitis-associated CRC with poor prognoses. Therefore, targeting the cancer-associated inflammation may offer new avenues for cancer treatment. In fact, several anti-inflammatory drugs, have been used for prophylaxis and have shown efficacy in contrasting cancer, despite various adverse side effects. Thus, there is an urgent need to discover novel cancer-associated mechanisms to develop alternative therapies that may reduce aberrant inflammatory responses without interfering with physiological defenses against infection and functional anti-tumor immunity. A novel approach promoting anti-tumor immunity has been recently proposed after the discovery of potent, endogenous, specialized pro-resolving mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, mainly derived from omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) via COX, LOX and CYP450 pathways, mediated by MFSD2A. Due to the potent bioactivity of SPMs in resolving inflammation and because of the correlation between inflammation and cancer, the roles of these lipid mediators have attracted great attention for their potential therapeutic role in cancer treatment, including CRC. Nevertheless, the understanding of the endogenous mechanisms that limit the inflammatory response during CRC development is incomplete and requires further investigation.
Based on the preliminary results indicating that dysfunctional MFSD2A-dependent pro-resolving pathways may foster CRC development, the investigators aim to define the functional role of MFSD2A in orchestrating pro-resolving pathways in the intestinal endothelium of metastatic and not metastatic CRC patients.
This is a cross-sectional single-center observational study involving patients with CRC. The investigators will enroll 15 patients with colorectal cancer (CRC) stratified by tumor stage (T0 / T1-T4, M0 / M1, N0 / N1 / N2) undergoing surgery in the Gastroenterology and Digestive Endoscopy unit within Gastro Center (IRCCS Ospedale San Raffaele).
Human Intestinal Microvascular Endothelial Cells (HIMEC) will be generated from each sample of cancer surgical specimens, while the healthy cells will be derived from the healthy margins of the colorectal resection of the same CRC patients.
MFSD2A will be overexpressed or silenced and the investigators will evaluate its biological effects in both tumor-derived HIMECs and healthy tissue-derived HIMECs through transcriptomics and lipidomics analysis. The investigators will also exploit a possible novel therapy based on the delivery of MFSD2A encoding plasmid-conjugated liposomes.
| 108244 | ecrin-mdr-crc
Project description:IntroductionThere still remains a gap between those who conduct science and those who engage in educating others about health sciences through various forms of social media. Few empirical studies have sought to define useful practices for engaging in social media for academic use in the health professions. Given the increasing importance of these platforms, we sought to define good practices and potential pitfalls with help of those respected for their work in this new field.MethodsWe conducted a qualitative study, guided by constructivist grounded theory principles, of 17 emerging experts in the field of academic social media. We engaged in a snowball sampling technique and conducted a series of semi-structured interviews. The analytic team consisted of a diverse group of researchers with a range of experience in social media.ResultsUnderstanding the strengths of various platforms was deemed to be of critical importance across all the participants. Key to building online engagement were the following: 1) Culture-building strategies; 2) Tailoring the message; 3) Responsiveness; and 4) Heeding rules of online engagement. Several points of caution were noted within our participants' interviews. These were grouped into caveat emptor and the need for critical appraisal, and common pitfalls when broadcasting one's self.DiscussionOur participants were able to share a number of key practices that are central to developing and sharing educational content via social media. The findings from the study may guide future practitioners seeking to enter the space. These good practices support professionals for effective engagement and knowledge translation without being harmed.
| S-EPMC7439800 | biostudies-literature
Project description:Super-resolution microscopy is transforming our understanding of biology but accessibility is limited by its technical complexity, high costs and the requirement for bespoke sample preparation. We present a novel, simple and multi-color super-resolution microscopy technique, called translation microscopy (TRAM), in which a super-resolution image is restored from multiple diffraction-limited resolution observations using a conventional microscope whilst translating the sample in the image plane. TRAM can be implemented using any microscope, delivering up to 7-fold resolution improvement. We compare TRAM with other super-resolution imaging modalities, including gated stimulated emission deletion (gSTED) microscopy and atomic force microscopy (AFM). We further developed novel 'ground-truth' DNA origami nano-structures to characterize TRAM, as well as applying it to a multi-color dye-stained cellular sample to demonstrate its fidelity, ease of use and utility for cell biology.
| S-EPMC4731806 | biostudies-literature
Project description:Utilizing renewable lignocellulosic resources for wastewater remediation is crucial to achieving sustainable social development. However, the resulting by-products and the synthetic process characterized by complexity, high cost, and environmental pollution limit the further development of lignocellulose-based materials. Here, we developed a sustainable strategy that involved a new functional deep eutectic solvent (DES) to deconstruct industrial xylose residue into cellulose-rich residue with carboxyl groups, lignin with carboxyl and quaternary ammonium salt groups, and DES effluent rich in lignin fragments. Subsequently, these fractions equipped with customized functionality were used to produce efficient wastewater remediation materials in cost-effective and environmentally sound manners, namely, photocatalyst prepared by carboxyl-modified cellulose residue, biochar-based adsorbent originated from modified lignin, and flocculant synthesized by self-catalytic in situ copolymerization of residual DES effluent at room temperature. Under the no-waste principle, this strategy upgraded the whole components of waste lignocellulose into high-value-added wastewater remediation materials with excellent universality. These materials in coordination with each other can stepwise purify high-hazardous mineral processing wastewater into drinkable water, including the removal of 99.81% of suspended solids, almost all various heavy metal ions, and 97.09% chemical oxygen demand, respectively. This work provided promising solutions and blueprints for lignocellulosic resources to alleviate water shortages while also advancing the global goal of carbon neutrality.
| S-EPMC10993153 | biostudies-literature
Project description:BackgroundThe magnitude of the perioperative inflammatory response plays a role in surgical outcomes. However, few studies have explored the mechanisms of the resolution of inflammation in the context of surgery. Here, we described the temporal kinetics of interleukin-6, cortisol, lipoxin A4, and resolvin D in patients who underwent oncologic liver resections.MethodsAll patients gave written informed consent. Demographic and perioperative surgical data were collected, along with blood samples, before surgery and on the mornings of postoperative days 1, 3, and 5. Interleukin-6, cortisol, lipoxin-A4, and resolvin D were measured in plasma. A P value < 0.05 was considered statistically significant.ResultsForty-one patients were included in the study. Liver resection for colorectal metastatic disease was the most commonly performed surgery. The plasma concentrations of interleukin-6 were highest on day 1 after surgery and remained higher than the baseline up to postoperative day 1. Postoperative complications occurred in 14 (24%) patients. Cortisol concentrations spiked on postoperative day 1. The concentrations of lipoxin A4 and resolvin D were lowest on day 1 after surgery.ConclusionsThe inflammatory response associated with hepatobiliary surgery is associated with low circulating concentrations of lipoxin A4 and resolvin D that mirror, in an opposite manner, the kinetics of interleukin 6 and cortisol.Trial registrationNCT01438476.
| S-EPMC5556621 | biostudies-literature