scholarly journals Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

2021 ◽  
Author(s):  
Suhyun Kim ◽  
Eun-Hye Hong ◽  
Cheol-Ki Lee ◽  
Yiseul Ryu ◽  
Hyunjin Jeong ◽  
...  
Keyword(s):  
Comprehensive Evaluation ◽  
Enzymatic Reaction ◽  
Therapeutic Benefit ◽  
Biologically Active ◽  
Acute Colitis ◽  
Inflammatory Cytokine Production ◽  
Interleukin 22 ◽  
Transcription 3 ◽  
Potential Therapeutic Benefit

Interleukin-22 (IL-22), a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The potential therapeutic benefit of IL-22 is expected to be exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and a non-functional dimer. Monomeric IL-22 (mIL-22) was highly purified through a series of three separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate signal transducer and activator of transcription 3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

scholarly journals The Development of Integrin Alpha-8 Deficient Lungs Shows Reduced and Altered Branching and a Correction of the Phenotype During Alveolarization

2020 ◽  
Vol 11 ◽  
Author(s):  
Tiziana P. Cremona ◽  
Andrea Hartner ◽  
Johannes C. Schittny
Keyword(s):  
Lung Development ◽  
Therapeutic Benefit ◽  
Beta Subunits ◽  
Wild Type ◽  
Mouse Tissues ◽  
Spontaneous Contractions ◽  
Extracellular Matrix Receptors ◽  
Stereological Investigation ◽  
Potential Therapeutic Benefit

Lung development involves epithelial–mesenchymal interactions and integrins represent one of the key elements. These extracellular matrix receptors form hetero-dimers of alpha and beta subunits. The integrin α8β1 is highly expressed in mouse tissues, including lung. It forms a cellular receptor for fibronectin, vitronectin, osteopontin, nephronectin, and tenascin-C. This study aims to investigate the role of the integrin α8-subunit (α8) during lung development. Wild type and α8-deficient lungs were explanted at embryonic days 11.5/12.5. After 24–73 h in culture α8-deficient lung explants displayed reduced growth, reduced branching, enlarged endbuds, altered branching patterns, and faster spontaneous contractions of the airways as compared to wild type. Postnatally, a stereological investigation revealed that lung volume, alveolar surface area, and the length of the free septal edge were significantly reduced in α8-deficient lungs at postnatal days P4 and P7. An increased formation of new septa in α8-deficient lungs rescued the phenotype. At day P90 α8-deficient lungs were comparable to wild type. We conclude that α8β1 takes not only part in the control of branching, but also possesses a morphogenic effect on the pattern and size of the future airways. Furthermore, we conclude that the phenotype observed at day P4 is caused by reduced branching and is rescued by a pronounced formation of the new septa throughout alveolarization. More studies are needed to understand the mechanism responsible for the formation of new septa in the absence of α8β1 in order to be of potential therapeutic benefit for patients suffering from structural lung diseases.

scholarly journals Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3

Hepatology ◽  
2010 ◽  
Vol 52 (4) ◽  
pp. 1291-1300 ◽  
Author(s):  
Sung Hwan Ki ◽  
Oygi Park ◽  
Mingquan Zheng ◽  
Oriol Morales-Ibanez ◽  
Jay K. Kolls ◽  
...  
Keyword(s):  
Liver Injury ◽  
Murine Model ◽  
Alcoholic Liver Injury ◽  
Signal Transducer ◽  
Interleukin 22 ◽  
Ethanol Feeding ◽  
Transcription 3 ◽  
Binge Ethanol

Prognosticating role of serum eosinophils on immunotherapy efficacy in patients with advanced melanoma

Immunotherapy ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Adi Kartolo ◽  
Ryan Holstead ◽  
Wilma Hopman ◽  
Tara Baetz
Keyword(s):  
Retrospective Study ◽  
Therapeutic Benefit ◽  
Advanced Melanoma ◽  
Interval Time ◽  
Start Date ◽  
Peripheral Eosinophil ◽  
Potential Therapeutic Benefit ◽  
Eosinophil Counts

Aim: To evaluate serum eosinophilia (≥500 peripheral eosinophil counts/microliter) in prognosticating immunotherapy (IO) efficacy. Methodology: A retrospective study of 86 patients with advanced melanoma on PD-1 inhibitors. Results: Eosinophilia-on-IO was an independent prognosticating factor for median OS (HR :0.223; 95% CI: 0.088–0.567; p = 0.002). ‘Late eosinophilia’ (≥1 year from IO start date) group had better median OS (31.9 vs 24.1 vs 13.0 months; p = 0.002) when compared with ‘early eosinophilia’ (<1 year from IO start date) and ‘no eosinophilia’ groups, respectively. Conclusion: Eosinophilia-on-IO and its timing were associated with better IO efficacy in patients with advanced melanoma. Our findings provided insights on potential therapeutic benefit of inducing eosinophilia at certain interval time to obtain a longer durable immunotherapy response.

Anti-Hypertensive Potential and Epigenetics of Angiotensin II type 2 Receptor (AT2R)

2020 ◽  
Vol 16 ◽  
Author(s):  
Mayank Chaudhary
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Blood Pressure Regulation ◽  
Biologically Active ◽  
Pressure Regulation ◽  
Tissue Remodelling ◽  
Critical Pathway

Background:: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang aII), is biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation whereas AT2R is primarily involved in wound healing and tissue remodelling. Objective:: Recent studies have highlighted additional role of AT2R to counter balance detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as novel therapeutic target against hypertension. Conclusion:: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms including DNA methylation and histone modification have been explored vastly with relation to cancer but role of such mechanisms on expression of AT2R has recently gained interest.

scholarly journals Reconstitution in Proteoliposomes of the Recombinant Human Riboflavin Transporter 2 (SLC52A2) Overexpressed in E. coli

2019 ◽  
Vol 20 (18) ◽  
pp. 4416 ◽  
Author(s):  
Lara Console ◽  
Maria Tolomeo ◽  
Matilde Colella ◽  
Maria Barile ◽  
Cesare Indiveri
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Risk Factor ◽  
Biologically Active ◽  
Suitable Model ◽  
Native Protein ◽  
E Coli ◽  
Few Data ◽  
Riboflavin Transport

Background: the SLC52A2 gene encodes for the riboflavin transporter 2 (RFVT2). This transporter is ubiquitously expressed. It mediates the transport of Riboflavin across cell membranes. Riboflavin plays a crucial role in cells since its biologically active forms, FMN and FAD, are essential for the metabolism of carbohydrates, amino acids, and lipids. Mutation of the Riboflavin transporters is a risk factor for anemia, cancer, cardiovascular disease, neurodegeneration. Inborn mutations of SLC52A2 are associated with Brown-Vialetto-van Laere syndrome, a rare neurological disorder characterized by infancy onset. In spite of the important metabolic and physio/pathological role of this transporter few data are available on its function and regulation. Methods: the human recombinant RFVT2 has been overexpressed in E. coli, purified and reconstituted into proteoliposomes in order to characterize its activity following the [3H]Riboflavin transport. Results: the recombinant hRFVT2 showed a Km of 0.26 ± 0.07 µM and was inhibited by lumiflavin, FMN and Mg2+. The Riboflavin uptake was also regulated by Ca2+. The native protein extracted from fibroblast and reconstituted in proteoliposomes also showed inhibition by FMN and lumiflavin. Conclusions: proteoliposomes represent a suitable model to assay the RFVT2 function. It will be useful for screening the mutation of RFVT2.

scholarly journals The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin

2021 ◽  
Vol 22 (5) ◽  
pp. 2250
Author(s):  
Evita Athanasiou ◽  
Antonios N. Gargalionis ◽  
Fotini Boufidou ◽  
Athanassios Tsakris
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Comprehensive Evaluation ◽  
Tumor Development ◽  
Scientific Data ◽  
Malignant Brain Tumor ◽  
Direct Role ◽  
Tumor Pathology ◽  
Human Herpesviruses

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

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