Polymeric nanoparticles encapsulating novel TLR7/8 agonists as immunostimulatory adjuvants for enhanced cancer immunotherapy

Publication date: May 2018
Source:Biomaterials, Volume 164
Author(s): Hyunjoon Kim, Lin Niu, Peter Larson, Tamara A. Kucaba, Katherine A. Murphy, Britnie R. James, David M. Ferguson, Thomas S. Griffith, Jayanth Panyam
Cytotoxic T lymphocytes (CTLs) play a major role in cancer immunotherapy because of their ability to directly kill tumor cells and secrete tumor suppressive cytokines. Anticancer vaccines aim to provoke tumor-specific CTL responses, which require activation of antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages. Therefore, a potent immunostimulatory adjuvant capable of activating APCs is an essential component of anticancer vaccines. In this study, we introduce novel TLR 7/8 bi-specific agonists that significantly enhance cytokine secretion compared to TLR7 mono-selective compounds. Encapsulation of these TLR 7/8 agonists in poly(lactide-co-glycolide) (PLGA) nanoparticles increased the co-stimulatory molecule expression and antigen presentation via MHC I by DCs compared to the soluble agonist. When administered subcutaneously, these nanoparticles migrated to draining lymph node and triggered DC activation and expansion. This lead to expansion of antigen-specific CD8 T cells and enhanced CTL response, which resulted in significant prophylactic and therapeutic efficacy in melanoma, bladder and renal cell carcinoma tumor models. Importantly, our studies demonstrate significant reductions in systemic metastasis with the nanoparticle vaccine. Our results suggest novel TLR 7/8 agonist-encapsulated nanoparticles are potent immunostimulatory adjuvants for cancer immunotherapy.



http://ift.tt/2oTxXVB

Necroptotic cancer cells-mimicry nanovaccine boosts anti-tumor immunity with tailored immune-stimulatory modality

Publication date: May 2018
Source:Biomaterials, Volume 164
Author(s): Ting Kang, Yukun Huang, Qianqian Zhu, Hao Cheng, Yuanyuan Pei, Jingxian Feng, Minjun Xu, Gan Jiang, Qingxiang Song, Tianze Jiang, Hongzhuan Chen, Xiaoling Gao, Jun Chen
Recent breakthroughs in cancer immunotherapy offer new paradigm-shifting therapeutic options for combating cancer. Personalized therapeutic anti-cancer vaccines training T cells to directly fight against tumor cells endogenously offer tremendous benefits in working synergistically with immune checkpoint inhibitors. Biomimetic nanotechnology offers a versatile platform to boost anticancer immunity by efficiently co-delivering optimized immunogenic antigen materials and adjuvants to antigen presenting cells (APC). Necroptotic tumor cells can release danger associated molecule patterns (DAMPs) like heat shock proteins, being more immunogenic than naïve tumor cells. Here, nano-size "artificial necroptotic cancer cell" (αHSP70p-CM-CaP) composing of phospholipid bilayer and a phosphate calcium core was designed as a flexible vaccine platform for co-delivering cancer membrane proteins (CM), DAMPs signal-augmenting element α-helix HSP70 functional peptide (αHSP70p) and CpG to both natural killer (NK) cells and APC. Mechanically, immunogenic B16OVA tumor cells membrane-associated antigens and αHSP70p were reconstituted in artificial outer phospholipid bilayer membrane via one-step hydration and CpG encapsulated in the phosphate calcium core. The resulted αHSP70p-CM-CaP exhibited 30 nm in diameter with the immunogenic membrane proteins reserved in the particles to produce synergistic effect on bone marrow derived dendritic cells maturation and antigen-presentation. Following αHSP70p-CM-CaP vaccination, efficient lymph node trafficking and multi-epitope-T cells response was observed in mice. Vitally, αHSP70p-CM-CaP was also able to induce expansion of IFN-γ-expressing CD8⁺ T cells and NKG2D⁺ NK cells subsets. Most promisingly, αHSP70p-CM-CaP vaccination led to the killing of target cells and tumor regression in vivo when combined with anti-PD-1 antibody treatment on mice B16OVA melanoma models. Altogether, we demonstrated proof-of-concept evidence for the feasibility, capability and safety of a nanovaccine platform towards efficient personalized anticancer application.

Graphical abstract

http://ift.tt/2I9mkm0

Longitudinally extensive transverse myelitis following dengue virus infection: A rare entity

Sunil Malik, Sonal Saran, Archana Dubey, Ajay Punj

Annals of African Medicine 2018 17(2):86-89

Association of dengue fever with longitudinally extensive transverse myelitis in pediatric age group is a rare entity. We describe a case of 15 year old adolescent male who presented with dengue fever and in whom symptoms of transverse myelitis developed 4 weeks after fever (post-infectious stage). Magnetic resonance imaging confirmed the diagnosis of longitudinally extensive transverse myelitis involving dorso-lumbar cord. Patient recovered almost completely with minimal residual neurological deficit after a six weeks course of corticosteroids and supportive management including physiotherapy.

http://ift.tt/2FIoveA

Correlation of some predisposing intrinsic conditions with the morphological integrity of the Achilles tendon

Adegbenro Omotuyi John Fakoya, David Adeiza Otohinoyi, Francis Adelade Fakoya

Annals of African Medicine 2018 17(2):58-63

Background: Most studies have focused on ill-tendons with a little insight on how intrinsic factors correlate with the Achilles tendon (AT) morphology. Aim: This study aims at establishing how blood pressure (BP), blood glucose (BG), and body mass index (BMI) correlate with the morphology of the AT with emphasis on width changes. Materials and Methods: Participants were volunteers who were recruited during and after an organized health fair by the Medical Students' body of All Saints University, School of Medicine, Commonwealth of Dominica. A total of 336 people, consisting of 135 males and 201 females volunteered for the study. The most dominant age group was between 60 and 65 years. A self-administered questionnaire was used to acquire necessary information, and a preliminary clinical procedure was used to check for BP, BG, and BMI. Ultrasound examination was done in B-mode using a linear array high-frequency probe with a mediolateral approach at the AT. Results: Among the participants, 42.68%, 69.75%, and 30.38% had normal BP, BG, and BMI readings, respectively. BP, BG, and BMI statistically supported the hypothesis. Individuals with extreme BP, BG, and BMI had their AT width wider when compared with individuals with normal systemic readings. Sonographic examination revealed most participants with normal tendon morphology while some identifiable changes were observed among others. Conclusion: This study suggests that BP, BG, and BMI could affect the morphological integrity of the AT. It indicates that asymptomatic high blood sugar and BP could weaken the AT, leading to pain which may appear unrelated to the physician and patient.

http://ift.tt/2HvfWV4

Electroencephalography abnormalities in generalized epilepsy and their predictors: A multicenter experience

Lukman Femi Owolabi, Shehu Sale, Shakirah Desola Owolabi, Aisha Nalado, Muhammad Umar, Aminu Abdullahi Taura

Annals of African Medicine 2018 17(2):64-69

Background: In spite of the overwhelming significance of knowledge of basic elements of electroencephalography (EEG) in its application to the diagnostic workup and the management of patients with suspected or already established generalized epilepsy (GE), there is a dearth of data on the pattern and utility of clinical variables that can independently determine EEG abnormalities in GE. Objective: The study was designed to evaluate the frequency and pattern of EEG abnormality as well as assess the utility of clinical variables in predicting the likelihood of an abnormal EEG in GE. Methods: It was a cross-sectional study involving the analysis of EEGs of consecutive patients with clinical diagnosis of idiopathic GE from three centers over a 7-year period. Information on sociodemographic and seizure variables was obtained. The International Federation of Societies for Electroencephalography and Clinical Neurophysiology definition of interictal epileptiform discharges (interictal epileptiform activity [IEA]) was adopted in the study. Results: A total of 403 patients comprising 242 (60%) males and 161 (40%) females with clinical diagnosis of GE had EEG. Their age ranged between 2 weeks and 70 years, with a median age of 21 years and an interquartile age of 26 years. Two hundred and thirty-seven (58.8%) and 213 (52.9%) patients had abnormal EEG and IEA, respectively. Before adjustment for confounders, female gender (P = 0.0001), pediatric age group (P = 0.0388), duration of epilepsy of 1–4 years (P = 0.01387), uncontrolled seizure (P = 0.0060), and seizure frequency (P = 0.0001) were significantly associated with the presence of abnormal EEG. However, age, female gender, poor seizure control, and seizure frequencies were the independent predictors of EEG abnormality. Conclusion: The study showed that about 58% of patients with GE patients had abnormal EEG. Age, poor seizure control, and high frequency of seizure were independent predictors of the presence of EEG abnormality.

http://ift.tt/2HwJ8Lu

Concurrent giant tumoral pseudoangiomatous stromal hyperplasia necessitating bilateral mastectomy

Modupeola Omotara Samaila, Halima Oziohu Aliyu, Lazarus Mungu Yusufu, Shehu Abdullahi

Annals of African Medicine 2018 17(2):82-85

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign mesenchymal tumor of the breast. Majority occur as diffuse lesions, and diagnosis is often incidental or in a background of other breast pathologies. Bilaterality with multiple tumoral masses in giant breasts is a rarity. We report a 34-year-old nonlactating female with 2-year history of rapid progressive painless bilateral enlargement of the breasts following surgical excision of ill-defined breast lumps which were not subjected to histopathological evaluation a year earlier. Examination revealed bilateral nontender giant breasts extending to the umbilical area with masses which were not attached to overlying skin, Grade 2 pressure ulcers on the lateral posterior breast aspects bilaterally and peau d'orange. There were no other palpable masses or lymph nodes. A clinical assessment of bilateral gigantomastia was made. Bilateral mastectomy revealed giant PASH which was confirmed with positive immunohistochemical reactivity for CD34 and vimentin. No other breast pathologies were seen with extensive sectioning. Diffuse multiple breast lesions with incomplete excision are associated with rapid growth in PASH as seen in this case. The presence of concurrent bilateral giant tumoral masses without any underlying breast pathology is a novelty. The mainstay of treatment in this case is mastectomy despite its benign nature.

http://ift.tt/2FQQL28

A review of methods for measuring microplastics in aquatic environments

Abstract

An increasing number of reports have been published concerning microplastic (MP) pollution in aquatic environments. Methods used in these studies continue to be updated and lack standardization, so that an up-to-date review pertaining methods for MP research is needed. This critical review examines the analytical methods, including sampling, identification, and quantitation, for MP research. Samples are generally collected from water, sediment, and biota gastrointestinal tract. Manta nets or trawls are prevalently used in surface water sampling, while direct shoveling or box-corer grab are commonly applied in sediment sampling. Microplastics in biota are generally obtained by dissecting organisms and separating livers, gills, and guts. Density separation is frequently chosen to separate MPs from sample matrices. Chemical digestion can dissolve other organic materials and isolate MPs for further identification. Visual sorting should be combined with chemical composition analysis to better identify the polymer type. Pyrolysis or thermal decomposition gas chromatography coupled with mass spectrometry, Fourier transform infrared spectroscopy, and Raman spectroscopy are currently the main technologies for MP identification. Units prevalently used to express MP abundance in water, sediment, and biota are "particles per m³," "particles per m²," and "particles per individual," respectively. As MP abundances often varied with the methods used, we recommend that analytical protocols of MPs should better be standardized and optimized. Despite the important progress in analysis of MPs, detection technologies for identifying nano-sized plastic particles are still lacking, and therefore should be developed swiftly.

http://ift.tt/2GpW32C

Adsorption/desorption of arsenite and arsenate on chitosan and nanochitosan

Abstract

Equilibrium sorption studies of anionic species of arsenite, As(III) ions and arsenate As(V) ions onto two biosorbents, namely, chitosan and nanochitosan, have been investigated and compared. The results and trends in the sorption behavior are novel, and we have observed during the sorption process of the As(III) and As(V) on chitosan, a slow process of desorption occurred after an initial maximum adsorption capacity was achieved, before reaching a final but lower equilibrium adsorption capacity. The same desorption trend, however, is not observed on nanochitosan. The gradual desorption of As(III) and As(V) in the equilibrium sorption on chitosan is attributed to the different fractions of the dissociated forms of arsenic on the adsorbent surface and in solution and the extent of protonation of chitosan with the changing of solution pH during sorption. The change of solution pH during the sorption of arsenite ions on chitosan was also influenced by the interaction between the buffering effect of the arsenite species in the aqueous medium and the physical properties of chitosan. The final equilibrium adsorption capacity of chitosan for As(III) and As(V) was found to be around 500 and 8000 μg/g, respectively, whereas the capacities on nanochitosan are 6100 and 13,000 μg/g, respectively.

http://ift.tt/2tKUNo2

Integrating multi-source information on a single network to detect disease-related clusters of molecular mechanisms

Publication date: Available online 13 March 2018
Source:Journal of Proteomics
Author(s): Margarita Zachariou, George Minadakis, Anastasis Oulas, Sotiroula Afxenti, George M. Spyrou
The abundance of available information for each disease from multiple sources (e.g. as genetic, regulatory, metabolic, and protein–protein interaction) constitutes both an advantage and a challenge in identifying disease-specific underlying mechanisms. Integration of multi-source data is a rising topic and a great challenge in precision medicine and is crucial in enhancing disease understanding, identifying meaningful clusters of molecular mechanisms and increasing precision and personalisation towards the goal of Predictive, Preventive and Personalised Medicine (PPPM). The overall aim of this work was to develop a novel network-based integration methodology with the following characteristics: (i) maximise the number of data sources, (ii) utilise holistic approaches to integrate these sources (iii) be simple, flexible and extendable, (iv) be conclusive. Here, we present the case of Alzheimer's disease as a paradigm for illustrating our novel approach.SignificanceIn this work we present an integration methodology, which aggregates a large number of the available data sources and types by exploiting the holistic nature of network approaches. It is simple, flexible and extendable generating solid conclusions regarding the molecular mechanisms that underlie the input data. We have illustrated the strength of our proposed methodology using Alzheimer's disease as a paradigm. This method is expected to serve as a stepping-stone for further development of integration methods of multi-source omic-data and to contribute to progress towards the goal of Predictive, Preventive and Personalised Medicine (PPPM). The output of this methodology may act as a reference map of implicated pathways in the disease under investigation, where pathways related to additional omics data from any kind of experiment may be projected. This will increase the precision in the understanding of the disease and may contribute to personalised approaches for patients with different disease-related pathway profile, leading to a more precise, personalised and ideally preventive management of the disease.

Graphical abstract

http://ift.tt/2FQAr1b

Scholar : These new articles for Critical Discourse Studies are available online

The online platform for Taylor & Francis Online content New for Critical Discourse Studies and online now on Taylor & Francis Online: Original Articles 'See no evil, read no evil': the failing role of Turkish newspapers in coverage of Turkey's 2016 coup attempt Lyndon C. S. Way, Gökçen Karanfil & Aytunç Erçifci Pages: 1-19 | DOI: 10.1080/17405904.2018.1450277 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Editorial Board and Masthead

Publication date: March 2018
Source:Pediatric Neurology, Volume 80





http://ift.tt/2p9xwrb

Table of Contents

Publication date: March 2018
Source:Pediatric Neurology, Volume 80





http://ift.tt/2HuT5Ji

Meetings of Interest

Publication date: March 2018
Source:Pediatric Neurology, Volume 80





http://ift.tt/2p5sMTl

Scholar : Advances in Mental Health, Volume 16, Issue 1, April 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Advances in Mental Health, Volume 16, Issue 1, April 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Editorial Enhancing workforce capacity in mental health promotion, prevention and early intervention Andrea Reupert Pages: 1-4 | DOI: 10.1080/18387357.2018.1429196 Articles How 'mental health smart' are you? Analysis of responses to an Australian Broadcasting Corporation News website quiz Tessa L. Cutler, Nicola J. Reavley & Anthony F. Jorm Pages: 5-18 | DOI: 10.1080/18387357.2017.1317581 Non-participation in education, employment, and training among young people accessing youth mental health services: demographic and clinical correlates Erin M. Holloway, Debra Rickwood, Imogen C. Rehm, Denny Meyer, Scott Griffiths & Nic Telford Pages: 19-32 | DOI: 10.1080/18387357.2017.1342553 Consumer views on youth-friendly mental health services in South Australia Mark Loughhead, Sophie Guy, Gareth Furber & Leonie Segal Pages: 33-47 | DOI: 10.1080/18387357.2017.1360748 Experiences of a day treatment service using phenomenological analysis: 'Six weeks of little steps in the right direction' Rachel H. Tribe, Malgorzata Bielawska & Derek K. Tracy Pages: 48-64 | DOI: 10.1080/18387357.2017.1404432 Who do they think we are? Public perceptions of psychiatrists and psychologists Krisna Patel, Caroline Caddy & Derek K Tracy Pages: 65-76 | DOI: 10.1080/18387357.2017.1404433 Delivering a diploma of community services (alcohol and other drugs and mental health) in the remote town of Katherine (NT): a case study Xenia Girdler, Jocelyn Dhu & Anton Isaacs Pages: 77-87 | DOI: 10.1080/18387357.2017.1410437 Consumer-provider relationships in a care coordination model of service: consumer perspectives Richard Schweizer, Anne Honey, Nicola Hancock, Bridget Berry, Shifra Waks & Justin Newton Scanlan Pages: 88-100 | DOI: 10.1080/18387357.2018.1425095 2018 Future Directions Forum JOIN US at the 2018 Future Directions Forum for Journal of Clinical Child & Adolescent Psychology - June 15-16, 2018 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

MCM-2 expression differentiates potentially malignant verrucous lesions from oral carcinomas

Publication date: Available online 13 March 2018
Source:Annals of Diagnostic Pathology
Author(s): Kochli Channappa Niranjan, Niharika Abhay Sarathy, Devendra Alrani
BackgroundMcm-2 is a biomarker belonging to Mcm family of proteins which has rarely been used in oral potentially malignant and malignant lesions of the verrucous type. The objective of this study is to assess the expression of Mcm-2 in Normal Oral Mucosa (NM), Verrucous Hyperplasia (VH), Verrucous Carcinoma (VC) and Oral Squamous Cell Carcinoma (OSCC) and compare it with the clinicopathological characteristics.MethodologyA total of 70 formalin fixed paraffin embedded tissue samples (10 cases of Normal Mucosa NM- Group A, 10 cases of Verrucous Hyperplasia- VH without Dysplasia- Group B, 10 cases of Verrucous Hyperplasia- VH with Dysplasia- Group C, 20 cases of Verrucous Carcinoma VC-Group D, 20 cases of Oral Squamous Cell Carcinoma OSCC- Group E) were subjected to immunohistochemistry with Mcm-2 antibody. Statistical analysis was carried out with various tests like ANOVA, Tukey HSD, Chi-Square and Shapiro-Wilk test by using the SPSS software.ResultsThere was a significant difference in Mcm-2 expression with quantitative analysis among all the groups (p < 0.05). There was a significant progressive increase in nuclear Labelling Indices (nLI) from NM (49.08%), VC (60.45%), VH with Dysplasia (64.10%), and OSCC (89.22%).ConclusionThe findings suggest that Mcm-2 may be a sensitive proliferation marker in oral potentially malignant and malignant lesions which may be useful for differentiating between VH with/ without dysplasia, VC and OSCC.



http://ift.tt/2Iqs6Qy

Scholar : Studies in Chinese Religions, Volume 3, Issue 4, December 2017 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Studies in Chinese Religions, Volume 3, Issue 4, December 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Article The 'biography' of a Buddha image: the transformation of the lore for a stone image of Maitreya in Shicheng Jinhua Chen Pages: 307-349 | DOI: 10.1080/23729988.2018.1429139 'Circles of light' and 'treasure ships' in the Visualizing Amitāyus Tableaux: with a focus on some cases in Sichuan from the Tang and Five Dynasties period Mingli Sun Pages: 350-388 | DOI: 10.1080/23729988.2018.1429144 Book review China, Christianity, and the question of culture Marián Gálik Pages: 389-393 | DOI: 10.1080/23729988.2018.1429142 The Chinese Jews of Kaifeng: a millennium of adaptation and endurance Elijah Teitelbaum Pages: 394-396 | DOI: 10.1080/23729988.2018.1429133 Routledge Psychology 2017 sponsor of BPS #PsychCrunch podcasts. Access 25 journal articles: http://bit.ly/psychcrunch2017 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Editorial Board

Publication date: April 2018
Source:Critical Reviews in Oncology/Hematology, Volume 124





http://ift.tt/2pbTusr

Scholar : These new articles for CoDesign are available online

The online platform for Taylor & Francis Online content New for CoDesign and online now on Taylor & Francis Online: Original Articles Materiality in probes: three perspectives for co-exploring patient democracy Eva Knutz, Thomas Markussen & Signe Mårbjerg Thomsen Pages: 1-21 | DOI: 10.1080/15710882.2018.1445759 2018 Future Directions Forum JOIN US at the 2018 Future Directions Forum for Journal of Clinical Child & Adolescent Psychology - June 15-16, 2018 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Validation conform ISO-15189 of assays in the field of autoimmunity: Joint efforts in The Netherlands

Publication date: Available online 13 March 2018
Source:Autoimmunity Reviews
Author(s): Leontine Mulder, Renate van der Molen, Carin Koelman, Ester van Leeuwen, Anja Roos, Jan Damoiseaux
ISO 15189:2012 requires validation of methods used in the medical laboratory, and lists a series of performance parameters for consideration to include. Although these performance parameters are feasible for clinical chemistry analytes, application in the validation of autoimmunity tests is a challenge. Lack of gold standards or reference methods in combination with the scarcity of well-defined diagnostic samples of patients with rare diseases make validation of new assays difficult. The present manuscript describes the initiative of Dutch medical immunology laboratory specialists to combine efforts and perform multi-center validation studies of new assays in the field of autoimmunity. Validation data and reports are made available to interested Dutch laboratory specialists.



http://ift.tt/2HxZXpr

Short chain fatty acid, acetate ameliorates sepsis-induced acute kidney injury by inhibition of NADPH oxidase signaling in T cells

Publication date: May 2018
Source:International Immunopharmacology, Volume 58
Author(s): Naif O. Al-Harbi, Ahmed Nadeem, Sheikh F. Ahmad, Moureq R. Alotaibi, Abdullah F. AlAsmari, Wael A. Alanazi, Mohammad M. Al-Harbi, Ahmad M. El-Sherbeeny, Khalid E. Ibrahim
Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues. However, the role of acetate on T cell NADPH oxidase (NOX2)/ROS signaling remains unexplored during sepsis-induced AKI. Therefore, the current study investigated the effect of acetate on sepsis-induced AKI parameters and T cell oxidant-antioxidant balance. Our results show that acetate ameliorates sepsis-induced AKI as reflected by a decrease in serum, creatinine/blood urea nitrogen and renal myeloperoxidase activity/lipid peroxides and restoration of kidney tubular structure. Moreover, acetate administration was associated with correction of oxidant-antioxidant imbalance in T cells during sepsis-induced AKI. Acetate produced its inhibitory effects on NOX2/ROS signaling via attenuation of histone deacetylase activity in T cells which was induced during AKI. Overall, the data suggest that acetate might be beneficial during sepsis-induced AKI by restoration of oxidant-antioxidant balance in T cells.



http://ift.tt/2pfr6Gf