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The incidence of renal diseases continues to rise worldwide and as a consequence, increasing number of renal patients will probably require oral healthcare. Renal osteodystrophy refers to the wide spectrum of bone diseases in context to chronic renal diseases (CRD). Radiographic alterations affecting the jaws and facial skeleton are common and among the earliest signs of renal bone diseases. The aim of the present study is to review and highlight the various radiographic alterations affecting the maxillofacial region in renal osteodystrophy and enabling the general and specialty oral physicians to identify and diagnose them effectively. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are heterogeneous cell populations represented by different subtypes, each varying in terms of gene expression patterns and specific functions. Recent studies identified transcription factors essential for the development of different DC subtypes, yet molecular mechanisms for the developmental program and functions remain poorly understood. In this study, we developed and characterized a mouse DC progenitor-like cell line, designated DC9, from Irf8-/- bone marrow cells as a model for DC development and function. Expression of Irf8 in DC9 cells led to plasmacytoid DCs andCD8α+ DC-like cells, with a concomitant increase in plasmacytoid DC- and CD8α+ DC-specific gene transcripts and induction of type I IFNs and IL12p40 following TLR ligand stimulation. Irf8 expression in DC9 cells led to an increase in Id2 and Batf3 transcript levels, transcription factors shown to be important for the development of CD8α+ DCs. We show that, without Irf8, expression of Id2 and Batf3 was not sufficient for directing classical CD8α+ DC development. When coexpressed with Irf8, Batf3 and Id2 had a synergistic effect on classical CD8α+ DC development. We demonstrate that Irf8 is upstream of Batf3 and Id2 in the classical CD8α+ DC developmental program and define the hierarchical relationship of transcription factors important for classical CD8α+ DC development. [ABSTRACT FROM AUTHOR]

Ischaemia-reperfusion (IR) injury is known to be a risk factor influencing both short and long-term graft function following transplantation. The pathophysiology of IR injury is suggested to involve elevated reactive oxygen species production resulting in oxidative damaged cellular macromolecules.The objective of this study was to evaluate oxidative damage following IR using an isolated organ perfusion model of the transplanted kidney, in order to determine a simple, preferably non-invasive biomarker for IR injury.Porcine kidneys were retrieved with 10 or 40 min warm ischaemic (WI) time and haemoperfused for 6 h on an isolated organ perfusion machine. ELISA was used to detect carbonyls, 8-isporostane and 8-hydroxy-2′-deoxyguanosine, representing protein, lipid and DNA damage respectively in pre and post reperfusion samples of plasma, urine and biopsy material.Plasma carbonyl and 8-isporostane and were significantly increased in the 40 min group compared to pre-perfusion (0.96 ± 0.10 vs. 0.62 ± 0.06, P < 0.001 and 1.57(1.28–4.9) vs. 0.36(0.09–0.59), P < 0.05). The levels also correlated with creatinine clearance used to determine renal function (r = - 0.6150, P < 0.01 and r = - 0.7727, P < 0.01).The results of this study suggest both plasma carbonyl and 8-isporostane to be reliable biomarkers to predict the level IR injury. [ABSTRACT FROM AUTHOR]

Ethnomedicine is the study of traditional medicines having relevant written sources (Ayurveda, traditional Chinese Medicine) as well as those whose knowledge and practices have been orally transmitted over the centuries. The Neem tree (Azadirachta indica) has been known as the wonder tree for centuries in the Indian subcontinent. It has become important in the global context today because it offers solutions to the multiple concerns faced by mankind. Each part of the Neem tree has some medicinal property and the broad range of biologic activities and pharmacologic actions of Neem tree are very well established. Although literature search reveals that Neem tree has multiple potential uses in dentistry, its application is limited in routine dental practice. The following manuscript is an attempt to throw light on the potential and immense uses of Neem tree products for oral care, which forms a critical issue in both developing countries where professional dental care is limited and in developed nations where populations are aging. [ABSTRACT FROM AUTHOR]

• RP-HPLC method for mesalamine (Mes) and curcumin (Cur) was developed • The developed method was validated as per ICH Q2 (R1) guidelines • Recovery above 95% and % RSD less than 2 indicated about accuracy and precision of method • Absence of interfering peaks at the retention times of Mes and Cur indicated method's specificity • The method was used to find drug loading, entrapment efficiency and drug release in Nano Structured Lipid Carriers The aim of this study was to develop simple, advance, accurate and precise method for the quantification of mesalamine (Mes) and curcumin (Cur) in nanostructured lipid carriers (NLCs) by using high Performance Liquid Chromatography (HPLC) technique. The analysis of the method was done by using C-18 Nucleodur column with 250 mm x 4.6 mm dimensions and having i.d. of 5µ. The quantification of Mes and Cur on HPLC was done by using mobile phase acetonitrile and water in the different ratios at different time intervals (gradient method), flow rate kept 1 mL/min and wavelength was set up at isosbestic point 365 nm. By using gradient method of ACN and water the peak of Mes and Cur was found to be at 1.7 min and 9.6 min respectively. The developed method was validated in accordance with ICH Q2 (R1) guidelines. The developed method showed linearity in the range of 2-10 ppm with r2 equals to 1 i.e 0.9998 for Mes and 0.9998 for Cur. The system suitability parameters of the method were also measured which were found to be tailing factor less than 2, resolution between Mes and Cur peaks was more than two and theoretical plates more than 2000. The LOD and LOQ of the developed method for Mes was found to be 0.14 µg/mL and 0.45 µg/mL. Whereas, LOD and LOQ of the developed method for Cur was found to be 0.17 µg/mL and 0.52 µg/mL respectively. The relative standard deviation of the developed method for both Mes and Cur were below 2 and percentage recovery was found to be between 95-105%. The robustness of the developed method was also checked by doing small changes in the flow rate and wavelength. The results of robustness study revealed that relative standard deviation and percentage recovery for both Mes and Cur were under acceptance criteria of ICH Q2 (R1) guidelines. This indicated that the method is precise, accurate, simple and robust. In addition, the developed method was effectively used for the estimation of entrapment efficiency (EE), drug loading (DL) and in vitro drug release study of Mes and Cur in the prepared Mes-Cur based NLCs. The EE of Mes and Cur in NLCs was found to be 99% and 84% respectively. Whereas, DL of Mes and Cur in the formulation was found to be 0.0019% and 0.0033% respectively. The in vitro drug release study showed that within 48h 100% Mes was released from NLCs. Whereas, 82.23% Cur was released from the NLCs. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs), are small non-coding RNAs of approximately 22 nucleotides in length, playing an important role in regulating gene expression post-transcriptionally. Understanding the effect of miRNA regulation in a pathway-specific manner unravels the approaches adopted to apprehend biological mechanisms, the information, which is scanty for researchers, not primed already for miR related research. Here, we describe a quick perspective in 5 steps with probable approaches and assays at every level to unravel the specific role of a microRNA, miR-145a-5p, as an example. This perspective as a guide would help in identifying novel targets for a microRNA, as shown for miR-145a-5p, which down-regulated the mRNA expression of ADD3 and BRCA2, using bioinformatic tools and experimental assays. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are a collection of different subtypes, each of which is characterized by specific surface markers, gene-expression patterns, and distinct functions. Members of the IFN regulatory factor family play critical roles in DC development and functions. Recently, Irf8 was shown to activate TGF-b signaling, which led to exacerbated neuroinflammation in the experimental autoimmune encephalomyelitis mouse model. We analyzed the effect of Irf8 on TGF-β/bone morphogenetic protein pathway-specific genes in DCs and identified Acvrl1, a type I TGF-β superfamily receptor, as a gene strongly induced by Irf8 expression. Among various DC subtypes, Acvrl1 is differentially expressed in CD8β+ DCs. ACVRL1 signaling augmented Irf8-directed classical CD8α+ DC development. Irf8 expression is essential for plasmacytoid DC and CD8α+ DC development, and this study demonstrates that ACVRL1 signaling plays a pivotal role whereby it suppresses plasmacytoid DC development while enhancing that of CD8α+ DCs, thus contributing to DC diversity development. [ABSTRACT FROM AUTHOR]

• Among TFs critical for cDC1 development, IRF8 interacts with BATF3 but not with ID2. • IRF8 and BATF3 together regulate distinct gene expression profiles in cDC1 subtype. • cDC1 displays enhanced expression of Pfkfb3 guided by IRF8 and BATF3. • PFKFB3 inhibition by PFK15 interferes with cDC1 development in murine model. Dendritic cells (DCs) play central role in innate as well as adaptive immune responses regulated by diverse DC subtypes that vary in terms of surface markers, transcriptional profile and functional responses. Generation of DC diversity from progenitor stage is tightly regulated by complex molecular inter-play between transcription factors. We earlier demonstrated that Batf3 and Id2 expression have a synergistic effect on the Irf8 directed classical cDC1 development. In present study, Bi-molecular fluorescence complementation assay suggested that IRF8 interacts with BATF3, and ID2 may aid cDC1 development independently. Genome wide recruitment analysis of IRF8 and BATF3 from different DC subtypes led to identification of the overlapping regions of occupancy by these two transcription factors. Further analysis of overlapping peaks of IRF8 and BATF3 occupancy in promoter region within the cDC1 subtype specific transcriptional pattern identified a metabolically important Pfkfb3 gene. Among various immune cell types; splenic cDC1 subtype displayed enhanced expression of Pfkfb3. Analysis of Irf8-/- , Irf8R294C and Batf3DCKO DC confirmed direct regulation of Pfkfb3 enhanced expression specifically in cDC1 subtype. Further we show that inhibition of PFKFB3 enzymatic activity by a chemical agent PFK15 led to reduction in cDC1 subtype in both in vitro FLDC cultures as well as in vivo mouse spleens. Together, our study identified the direct regulation of cDC1 specific enhanced expression of Pfkfb3 in glycolysis and cDC1 biology. [ABSTRACT FROM AUTHOR]

• RelB suppresses type I IFN signaling. • Suppression of type I IFN signaling by RelB is mediated IκBα. • RelB expression dampens antiviral responses by lowering ISGs. • The defect in cDC2 development in Relb−/− mice can be rescued in Ifnar1 null background. Type I Interferon (IFN) signaling plays a critical role in dendritic cell (DC) development and functions. Inhibition of hyper type I IFN signaling promotes cDC2 subtype development. Relb is essential to development of cDC2 subtype and here we analyzed its effect on type I IFN signaling in DCs. We show that Relb suppresses the homeostatic type I IFN signaling in cDC2 cultures. TLR stimulation of FL-DCs led to RelB induction coinciding with fall in IFN signatures; conforming with the observation Relb expression reduced TLR stimulated IFN induction along with decrease in ISGs. Towards understanding mechanism, we show that effects of RelB are mediated by increased levels of IκBα. We demonstrate that RelB dampened antiviral responses by lowering ISG levels and the defect in cDC2 development in RelB null mice can be rescued in Ifnar1−/− background. Overall, we propose a novel role of RelB as a negative regulator of the type I IFN signaling pathway; fine tuning development of cDC2 subtype. [ABSTRACT FROM AUTHOR]