The Multifaceted Interface Between Cytokines and microRNAs: An Ancient Mechanism to Regulate the Good and the Bad of Inflammation

MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNA molecules that affect gene expression by binding to target messenger RNAs and play a role in biological processes like cell growth, differentiation, and death. Different CD4+ T cell subsets such as Th1, Th2, Th17, and T regulatory cells, exert a distinct role in effector and regulatory-type immune responses. miRNAs have been shown to respond to dynamic micro-environmental cues and regulate multiple functions of T cell subsets including their development, survival and activation. Thus, miRNA functions contribute to immune homeostasis, on the one side, and to the control of immune tolerance, on the other. Among the most important proteins whose expression is targeted by miRNAs, there are the cytokines, that act as both key upstream signals and major functional outputs, and that, in turn, can affect miRNA level. Here, we analyze what is known about the regulatory circuit of miRNAs and cytokines in CD4+ T lymphocytes, and how this bidirectional system is dysregulated in conditions of pathological inflammation and autoimmunity. Furthermore, we describe how different T cell subsets release distinct fingerprints of miRNAs that modify the extracellular milieu and the inter-cellular communication between immune cells at the autocrine, paracrine, and endocrine level. In conclusion, a deeper knowledge of the interplay between miRNAs and cytokines in T cells may have pivotal implications for finding novel therapeutic strategies to target inflammation and autoimmune disorders

Therapeutic opportunities to modulate immune tolerance through the metabolism-chromatin axis

: The ability of the immune system to discriminate external stimuli from self-components - namely immune tolerance - occurs through a coordinated cascade of events involving a dense network of immune cells. Among them, CD4+CD25+ T regulatory cells are crucial to balance immune homeostasis and function. Growing evidence supports the notion that energy metabolites can dictate T cell fate and function via epigenetic modifications, which affect gene expression without altering the DNA sequence. Moreover, changes in cellular metabolism couple with activation of immune pathways and epigenetic remodeling to finely tune the balance between T cell activation and tolerance. This Review summarizes these aspects and critically evaluates novel possibilities for developing therapeutic strategies to modulate immune tolerance through metabolism via epigenetic drugs

Images of Violence from Mexico: A performance art based enquiry

The aims of this research have been: To create images and sculptures and explore their use in performative actions; To conduct a practice-based research project that examines how representations of human violence are explored through performance, while maintaining ethical value in aesthetic perception; and To develop a methodology in performance art through which I express my work as practice and the use of myself as a participant. These aims have been informed by the blurring of perceptions of space, authenticity, and notions of the global and local; by designing a theoretical framework informed by the concept of ‘Capitalismo Gore’; by traversing a methodology that juxtaposes the performer with images of violence from Mexico, situates the performer as a locus of tension between two different communities (Mexican and British), and engulfs the performer in affective responses to Mexican victims of violence. This art-practice based research is supported by a theoretical framework that refers to the term ‘Capitalismo Gore’ as the most relevant philosophical reference to address the narrative of extreme violence happening in Mexico during the war on drugs (Valencia, 2008). This art practice invites the readers to traverse a self-narrative constructed with feedback gathered from the audience and dialogues with artists and curators of a set of performance art methodologies. These performance art methodologies juxtapose the artist-scholar with images of violence from Mexico. Moreover, the affects produced by these performances have been transformed into visual documentation, some of them in the form of zines. Booklets are a simple way to show images and to distribute them among a wider audience. They are easy to transport and can be displayed in galleries, libraries, art fairs, book fairs. They demonstrate an important testimony for this research, situated as it is between two cultures, Mexican and British. The overall methodology not only appropriates performance methods such as Ewa Partum’s active poetry, but it also introduces them into an academic context and regenerates them by replacing Partum’s performance symbols with different symbols. The development of art practice-based research emphasises the need to avoid situating the performer in the place of the victims. It seeks at some moments to place the performer next to them, sharing part of their distress and hope through performance artistic practices and its documentation. The research has generated exploratory insights through the spatial aspect of my artistic practice, the spaces in which the performances occurred and the spaces generated by these performances

Leptin: Role of metabolism in the regulation of inflammation

Over the last few years the intricate interaction between immune system and adipose tissue has been recognized. Indeed, it has been suggested that adipose tissue is not only a mere site of lipid and energy storage but can be considered as an "immune-related" organ producing a series of molecules named adipokines. Among these, leptin, an adipocyte-derived cytokine-like hormone, seems to play a pivotal role in the regulation of several neuroendocrine and immune functions. In this review, we describe the effects of leptin in inflammation and immunity, and speculate on the possible modulation of the leptin axis in novel adipopharmacotherapeutic settings.Biomedical Reviews 2006; 17: 53-62

SISTEM INFORMASI MANAJEMEN UMAT KATOLIK KEUSKUPAN BANDUNG

Setelah dokumen dan kelengkapan Proposal Kegiatan Pengabdian Kepada Masyarakat dengan judul Sistem Informasi Manajemen Umat (SIMU) Keuskupan Bandung, disetujui oleh Pimpinan LPPM Unpar, maka proses pembangunan SIMU pun dilakukan. Kegiatan sepanjang tahun 2015 merupakan kegiatan pembangunan SIMU, dan resmi diluncurkan pada saat acara Sinode Keuskupan Bandung, oleh Uskup Bandung, 22 November 2015 di Lembang.SIMU dibangun setelah melakukan tahap analisis kebutuhan sistem, menggunakan teknik survey pengamatan, wawancara, dan analisis dokumen saat kini. Kemudian dirancang bagan aliran kerja dan prosedur SIMU sesuai spesifikasi para pengguna SIMU. Pembangunan perangkat lunak SIMU diawali dengan analisis kebutuhan perangkat lunak, menggunakan usecase Diagram dan Entity-Relation Diagram. Pada tahap perancangan, dirancang antarmuka sistem, perancangan fisik basisdata, pengkodena program menggunakan framework Odoo, serta perancangan arsitektur jaringan (berbasis web).SIMU disosialisasikan melalui rapat rutin per tiga bulan dengan pimpinan keuskupan dan tiga kali pertemuan dengan para pastor se keuskupan di Pratista. SIMU telah diujicobakan di dua paroki di Bandung (Odilia dan Ignatius) selama dua minggu. Telah dilakukan pelatihan bagi para staf sekretariat paroki yang kelak akan berperan sebagai Admin Paroki dalam SIMU. Pada acara Sinode 22 November 2015, Uskup Bandung akan meresmikan SIMU.Selanjutnya, sejak Desember 2015 dan selama Januari-Juni 2016, sosialisasi SIMU secara langsung ke setiap dekenat dilakukan. Setiap paroki harus melakukan migrasi data PISA ke dalam SIMU, dan transaksi data umat beralih menggunakan SIMU, paling lambat pada Juni 2016. Sepanjang tahun 2016 akan dilakukan evaluasi dan perawatan SIMU berdasarkan kendala dan kebutuhan baru yang muncul

Ophthalmic Solutions with a Broad Antiviral Action: Evaluation of Their Potential against Ocular Herpetic Infections

HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new cases exhibiting serious visual failures. Generally, the therapy uses antiviral drugs to promote healing; however, there are currently no compounds that are able to completely eradicate the virus. In addition, the phenomenon of resistance is rapidly spreading among HSV-1 strains, creating mutants developing resistance to the common antiviral drugs; therefore, deep research on this issue is warranted. The efficacy of different ophthalmic solutions already on the market was evaluated for reducing HSV-1 infection. Different plaque assays were set up on epithelial cells, revealing that two ophthalmic solutions were able to inhibit viral replication in the early stages of infection. The data were further confirmed by molecular tests analyzing the expression levels of the principal genes involved in HSV-1 infection, and a strong reduction was observed after only 1 min of eye-drop treatment. Collectively, these results suggested the use of ophthalmic solutions as potential antiviral options for the treatment of ocular herpetic infection

Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1−/− Mouse

Insulin-like growth factor 1 (IGF-1) is a powerful regulator of synaptic activity and a deficit in this protein has a profound impact on neurotransmission, mostly on excitatory synapses in both the developing and mature auditory system. Adult Igf1−/− mice are animal models for the study of human syndromic deafness; they show altered cochlear projection patterns into abnormally developed auditory neurons along with impaired glutamate uptake in the cochlear nuclei, phenomena that probably reflect disruptions in neuronal circuits. To determine the cellular mechanisms that might be involved in regulating excitatory synaptic plasticity in 4-month-old Igf1−/− mice, modifications to neuroglia, astroglial glutamate transporters (GLTs) and metabotropic glutamate receptors (mGluRs) were assessed in the cochlear nuclei. The Igf1−/− mice show significant decreases in IBA1 (an ionized calcium-binding adapter) and glial fibrillary acidic protein (GFAP) mRNA expression and protein accumulation, as well as dampened mGluR expression in conjunction with enhanced glutamate transporter 1 (GLT1) expression. By contrast, no differences were observed in the expression of glutamate aspartate transporter (GLAST) between these Igf1−/− mice and their heterozygous or wildtype littermates. These observations suggest that congenital IGF-1 deficiency may lead to alterations in microglia and astrocytes, an upregulation of GLT1, and the downregulation of groups I, II and III mGluRs. Understanding the molecular, biochemical and morphological mechanisms underlying neuronal plasticity in a mouse model of hearing deficits will give us insight into new therapeutic strategies that could help to maintain or even improve residual hearing when human deafness is related to IGF-1 deficiency