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Modification of the extracellular matrix (ECM) is a critical aspect of developing a metastasis-supportive organ niche. Recent work investigating ECM changes that facilitate metastasis has revealed ways in which different metastatic organ niches are similar as well as the distinct characteristics that make them unique. In this review, we present recent findings regarding how ECM modifications support metastasis in four frequent metastatic sites: the lung, liver, bone, and brain. We discuss ways in which these modifications are shared between metastatic organs as well as features specific to each location. We also discuss areas of technical innovation that could be advantageous to future research and areas of inquiry that merit further investigation.

Systemic inflammation is known to be a key component of infection and non-infection diseases progression and may lead to multiorgan failure, persistent inflammation, immunosuppression, catabolism syndrome or even indolent death. This importance dictates the need for relevant in vivo models of inflammation to investigate the pathogenesis of numerous diseases and to perform drug screening. Danio rerio (zebrafish) became one of the most important models to explore biological processes in vivo. The aim of the study was to generate a lipopolysaccharide (LPS) model of systemic inflammation in vivo using zebrafish and to identify organspecific proinflammatory genes activity after intraperitoneal LPS infusion. We performed organ specific analysis of main proinflammatory genes expression in zebrafish after LPS stimulation. Comparing 18s, eef1a1l1, gapdh, and actb as potential housekeeping genes, we came to conclusion that eef1a1l1 with 99% effectiveness is the most promising for further normalization in this model. The genes activity was the most pronounced in the heart where the expression of IL6, CXCL8a, and CXCL18β was increased up to 100-fold. Moreover, the kidneys were the most involved in the inflammatory process since the highest number of analysed genes were up-regulated there: expression levels of CXCL18β, CXCL8a, IL1β, IL6, Mpeg1.2, and TNFa were significantly increased. This was probably related to the kidney activity as an immune and hematopoietic organ. The lowest reactivity was detected in the muscles. Immune reactions could be dose-dependent, for instance the infusion of 20 µg LPS led to decrease of expression of IFNy, Mpeg 1.2, and Mpeg 1.1 in the liver and to increase of Mpeg 1.2 expression in the kidney comparing with 10 µg dosage. Thus, due to the high degree of the similarity and other unique properties, Danio rerio has the advantage of being relevant model of inflammation. Our model demonstrated that the investigation of isolated zebrafish organs could be useful and informative for the investigation of inflammatory processes.

Wheat is one of the most consumed foods in the world. Although it is extremely nutrient rich for us humans, some of us have great difficulties in completely digesting its protein subunits. This review aims to understand the onset of Celiac Disease and its association with several other auto-immune diseases. The gliadin molecule, undigested in the small intestine, over time, ruptures the villi lining of the intestinal wall and enters the bloodstream which in turn activates the body's immune response. In some patients with the presence of HLA DQ2/DQ8 genes, this immune response results in Celiac Disease. Notably, researchers over the past several decades have found several links between Celiac Disease and multiple auto-immune diseases. Diabetes is one such auto-immune disease which has shown multiple associations with Celiac Disease. Similarly, in this review paper, we are critically analyzing the association of Celiac Disease with some of the most common autoimmune diseases namely Type-1 Diabetes, Multiple Sclerosis, Autism and Inflammatory Bowel Disease. In this paper, we have shown a clear correlation of celiac disease with several other auto-immune diseases. Further study is needed to understand the bidirectional association of Celiac Disease with different auto-immune diseases.

Organ-specificity of plant defense is an under-represented axis of research in plant biology. However, recent publications point out the importance of this concept in plant-pathogen interactions. I...

Background: Autoimmune diseases tend to cluster in the same individual or in families. Four types of autoimmune polyglandular syndromes (APS) have been described based on the combination of endocri...

Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each), mostly from the epithelia, of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although with variable extent, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes like SBS22 were found in different tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In epithelial tissues from esophagus and cardia, macroscopic somatic clones expanded to several millimeters were frequently seen, whereas in tissues from colon, rectum, and duodenum somatic clones were microscopic in size and evolved independently. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.

Introduction Accumulating data highlights that dysregulation of type I interferon (IFN) pathways plays a central role in the pathogenesis of several systemic and organ specific autoimmune diseases. Advances in understanding the role of type I IFNs in these disorders can lead to targeted drug development as well as establishing potential disease biomarkers. Areas covered Here, we summarize current knowledge regarding the role of type I IFNs in the major systemic, as well as organ specific, autoimmune disorders, including prominent inflammatory CNS disorders like multiple sclerosis. Expert opinion Type I IFN involvement and its clinical associations in a wide spectrum of autoimmune diseases represents a promising area for research aiming to unveil common pathogenetic pathways in systemic and organ specific autoimmunity.

Twenty-one accessions of Primula veris subsp. macrocalyx (Primulaceae) were chemically analyzed to clarify the presence of naturally rare macrocyclic bis-bibenzyls (BB). These compounds are typically found in liverworts but not known from higher plants, with the exception of the species under study. However, data are scarce concerning organ specific accumulation of BB in populations of the Primula. Comparative HPLC profiling of methanolic extracts of different parts of the plants revealed that these compounds are predominantly accumulated in the rhizome parts of the plant, in varying and sometimes quite small amounts. This is suggestive for a possible role as dihydrostilbenoid phytoalexins. Riccardin C was isolated as the main BB derivative, and its structure was elucidated on basis of NMR and mass spectral data, which is in alignment with earlier publications. In addition, cytotoxic bioassays of structurally related BB riccardin C, perrottetin F, perrottetin E, and marchantin A, were carried out against three human cancer cell lines, the non-small cell lung carcinoma – A549, the colon carcinoma – SW480, and the ovarian teratocarcinoma −CH1/PA‐1, respectively. Riccardin C and perrottetin E showed a pronounced activity in concentrations between 23–36 μM with low dependence on intrinsic resistance of the cell lines. These tests might be a useful basis for future research. The possible ecological role of BB accumulation in the rhizomes of Primula is briefly addressed.

This study investigated the prevalence rate, relative abundance and mean intensity of par­asites infecting cultured Nile tilapia Oreochromis niloticus L. in three fish farms, Gbarnga, Warta and CARI in Bong County, Liberia. Organs from thirty fish samples were exam­ined from September 2016 to February 2017, along with water quality parameters. Results showed the occurrence of seven parasites including protozoans, monogeneans, digeneans, cestodes, hirudineans, nematodes and crustaceans which were organ specific in terms of infection. The prevalence of the parasites varied seasonally, with the highest numbers oc­curring in November-January. The low prevalence rate, relative abundance and mean in­tensity of the parasites showed no threat to fish farmers in Liberia. All the water quality parameters were at desirable levels for the culture of the fish except nitrite, which was beyond the threshold for sustainable fish culture. It is therefore concluded that although parasitic infections in the three farms in the Bong County were low, best farm management practices are essential.

Objective This study aimed at assessing the risks associated with human exposure to heat-stress conditions by predicting organ- and tissue-level heat-stress responses under different exertional activities, environmental conditions, and clothing. Methods In this study, we developed an anatomically detailed three-dimensional thermoregulatory finite element model of a 50th percentile U.S. male, to predict the spatiotemporal temperature distribution throughout the body. The model accounts for the major heat transfer and thermoregulatory mechanisms, and circadian-rhythm effects. We validated our model by comparing its temperature predictions of various organs (brain, liver, stomach, bladder, and esophagus), and muscles (vastus medialis and triceps brachii) under normal resting conditions (errors between 0.0 and 0.5 °C), and of rectum under different heat-stress conditions (errors between 0.1 and 0.3 °C), with experimental measurements from multiple studies. Results Our simulations showed that the rise in the rectal temperature was primarily driven by the activity level (~ 94%) and, to a much lesser extent, environmental conditions or clothing considered in our study. The peak temperature in the heart, liver, and kidney were consistently higher than in the rectum (by ~ 0.6 °C), and the entire heart and liver recorded higher temperatures than in the rectum, indicating that these organs may be more susceptible to heat injury. Conclusion Our model can help assess the impact of exertional and environmental heat stressors at the organ level and, in the future, evaluate the efficacy of different whole-body or localized cooling strategies in preserving organ integrity.

Purpose Two‐dimensional (2D) IMRT QA has been widely performed in Radiation Oncology clinic. However, concerns regarding its sensitivity in detecting delivery errors and its clinical meaning have been raised in publications. In this study, a robust methodology of three‐dimensional (3D) IMRT QA using fiducial registration and structure‐mapping was proposed to acquire organ‐specific dose information. Methods Computed tomography (CT) markers were placed on the PRESAGE dosimeter as fiducials before CT simulation. Subsequently, the images were transferred to the treatment planning system to create a verification plan for the examined treatment plan. Patient’s CT images were registered to the CT images of the dosimeter for structure mapping according to the positions of the fiducials. After irradiation, the 3D dose distribution was read‐out by an optical‐CT (OCT) scanner with fiducials shown on the OCT dose images. An automatic localization algorithm was developed in MATLAB to register the markers in the OCT images to those in the CT images of the dosimeter. SlicerRT was used to show and analyze the results. Fiducial registration error was acquired by measuring the discrepancies in 20 fiducial registrations, and thus the fiducial localization error and target registration error (TRE) was estimated. Results Dosimetry comparison between the calculated and measured dose distribution in various forms were presented, including 2D isodose lines comparison, 3D isodose surfaces with patient’s anatomical structures, 2D and 3D gamma index, dose volume histogram and 3D view of gamma failing points. From the analysis of 20 fiducial registrations, fiducial registration error was measured to be 0.62 mm and fiducial localization error was calculated to be 0.44 mm. Target registration uncertainty of the proposed methodology was estimated to be within 0.3 mm in the area of dose measurement. Conclusions This study proposed a robust methodology of 3D measurement‐based IMRT QA for organ‐specific dose comparison and demonstrated its clinical feasibility.

Endothelial cells are at the interface between circulating blood and tissues. This position confers on them a crucial role in controlling oxygen and nutrient exchange and cellular trafficking between blood and the perfused organs. The endothelium adopts a structure that is specific to the needs and function of each tissue and organ and is subject to tissue-specific signalling input. In adults, endothelial cells are quiescent, meaning that they are not proliferating. Quiescence was considered to be a state in which endothelial cells are not stimulated but are instead slumbering and awaiting activating signals. However, new evidence shows that quiescent endothelium is fully awake, that it constantly receives and initiates functionally important signalling inputs and that this state is actively regulated. Signalling pathways involved in the maintenance of functionally quiescent endothelia are starting to be identified and are a combination of endocrine, autocrine, paracrine and mechanical inputs. The paracrine pathways confer a microenvironment on the endothelial cells that is specific to the perfused organs and tissues. In this Review, we present the current knowledge of organ-specific signalling pathways involved in the maintenance of endothelial quiescence and the pathologies associated with their disruption. Linking organ-specific pathways and human vascular pathologies will pave the way towards the development of innovative preventive strategies and the identification of new therapeutic targets., In this Review, Simons and colleagues present the current knowledge of organ-specific signalling pathways involved in the maintenance of endothelial quiescence and the pathologies associated with their disruption. This knowledge will assist the development of innovative preventive strategies and identification of new therapeutic targets., Key points Quiescent endothelial cells require active maintenance to preserve normalcy in a tissue-specific manner.Dysregulation of signalling pathways involved in endothelial normalcy maintenance leads to endothelial dysfunction and vascular pathologies.Endothelial quiescence and normalcy are important for disease resilience.Identification of organ-specific signalling pathways that maintain endothelial normalcy and quiescence will lead to new therapeutic targets supporting disease resilience and treatment of associated vascular pathologies.

Fumonisins, discovered in 1988 are a group of naturally occurring toxins produced by fusarium pathogenic fungi. Besides their presence in animal feeds, contamination of human foods such as corn, millet, oats, rye, barley, wheat and their products are widespread. Exposure to fumonisins results in species and organ specific toxicities including neurological disorders among equids, pulmonary edema in swine, esophageal cancer in humans and both kidney and liver related toxicities in rodents. This review seeks to consolidate groundbreaking research on the science of fumonisins toxicity, highlight recent progress on fumonisins research, and provide an overview of plausible mechanistic biomarkers for fumonisins exposure assessment.

Background: Fecal biomarkers (FCP) may be characterized by a superior diagnostic sensitivity as they are highly organ specific. Fecal calprotectin meets the criteria of a laboratory parameter suitable for the assessment of inflammatory bowel disease. Objective: To evaluate FCP levels in both preterm and full-term infants after start feeding and its relationship with the type of feeding, birth weight, and other clinical and laboratory parameters. Patients and Methods: This study was carried out at the outpatient clinic of the Pediatric Department Zagazig University Hospitals on 88 infants during the period from October 2016 to October 2017. Results: FCP levels increased in 100% of infants involved in the study after feeding. FCP levels have a wide range of variation from 82 to 425 µg/g before feeding and from 174 to 692 µg/g after feeding. A significant negative correlation between FCP levels before and after feeding with birth weight especially in the full-term group. A higher percentage of increase was observed in breastfeeding and ranged from 64.76 to 91.31%, while formula-fed feeding ranged from 39.09 to 84.94%. Conclusion: FCP levels increased in all infants after feeding with a wide range of variations with no differences between infants born vaginally or with C-section. The FCP levels increased significantly with breastfeeding than formula-fed feeding.

The phytochemistry of both bulbs and seeds of the ethnomedicinal Crinum stuhlmannii subsp. delagoense (Amaryllidaceae) was studied, sourced from a single location simultaneously. Eight alkaloids, including two previously unreported ones, N-methyl-haemanthamide (nivanine), and N-methyl-ent-delagoenine, were isolated along with lycorine, 8,9-methylenedioxophenanthridine, 6-hydroxycrinamine, 6-ethoxycrinamine, haemanthamine and hamayne. Compounds isolated were tested for acetylcholinesterase inhibition.

Carbon nanotubes are one of the most widely investigated carbon structures because of variety of physicochemical features offered by them. Their dimensions, surface chemistry and functionalization opportunities make them exceptional carrier for targeted drug delivery gene therapy, diagnosis and cell imaging. Both single and multi-walled CNTs have been functionalized for therapeutic applications. However, these structures have been associated with potential in vitro and in vivo cytotoxic effects. Such toxicities have been described to involve both cellular and subcellular mechanisms. Major organs that have shown significant CNTs related toxic effects include lungs, brain, heart, kidney, liver and skin. This review focuses on the potential toxicological effects of single and multi-walled carbon nanotubes and functionalization on these organs and associated mechanisms of toxicity

INTRODUÇÃO: A capsulite adesiva é uma condição dolorosa comum e debilitante da articulação glenohumeral que afeta cerca de 2 a 5% da população. Os órgãos internos e o sistema musculoesquelético são interligados por meio das membranas de sustentação. A tensão nessas membranas pode causar ainda mais restrições mecânicas, dor nas estruturas musculoesqueléticas e também restringir a mobilidade de órgãos viscerais. OBJETIVO: Explorar o efeito da manipulação visceral específica de órgãos na capsulite adesiva em pessoas afetadas no ombro direito. METODOLOGIA: Vinte indivíduos com capsulite adesiva foram avaliados para elegibilidade, dos quais 14 foram recrutados usando o método de amostragem por conveniência. Duas sessões de manipulação visceral comparada com manipulação placebo foram administradas nas primeiras duas semanas, seguidas de duas sessões de manipulação visceral do fígado nas duas semanas seguintes. O goniômetro digital, o nível de dor, a incapacidade no ombro e o esfigmomanômetro modificado foram usados para medir os resultados pré e pós intervenção. RESULTADOS: A comparação dos resultados entre os grupos mostrou uma diferença estatisticamente significativa nos escores de amplitude de movimentos [flexão (p = 0,001), rotação externa (p = 0,001), rotação interna (p = 0,001)], dor no ombro e escore do índice de incapacidade (0,004). Nenhuma mudança significativa foi observada no resultado de força. CONCLUSÃO: Duas sessões de manipulação visceral para o fígado podem ser benéficas na melhora da mobilidade do ombro direito, dor e incapacidade. O número de registro no Clinical Trial é 019/09/028271.

Objectives This study aimed to determine organ doses based on Monte Carlo (MC) simulations for individual patients undergoing routine adult chest abdomen-pelvis computed tomography (CT) examinations and to evaluate the correlations of organ doses with patient size and dose metrics. Methods MC simulations were performed by reading detailed descriptions of the CT scanner, scanning parameters, and CT images of phantoms and patients into the simulation software. The simulation models were validated by comparing the simulated doses with the doses measured by in-phantom dosimetry using radiophotoluminescent glass dosimeters and an adult anthropomorphic phantom, and organ doses for 80 patients were determined from the simulation results. To obtain patient size and dose metrics, body mass index and volume computed tomography dose index (CTDIvol) data were collected. Water equivalent diameter (WED) was calculated from the CT images of each patient. Size-specific dose estimates (SSDE) were calculated using CTDIvol and average WED over the scan range, and organ specific SSDE were calculated using the average CTDIvol and WED over each organ position. The correlations of organ doses with dose metrics were evaluated using coefficients of determination. Results Organ doses increased with patient size, and the doses for obese were approximately two to three times higher than those for underweight patients. Organ doses exhibited stronger linear relationships with organ specific SSDE (R2 ≥ 0.82) than other dose metrics. Conclusions The linear regression fits between organ doses determined by MC simulation and organ-specific SSDE are valuable for simplified and accurate organ dose estimation for individual patients undergoing CT examinations.

Purpose We aimed to predict and compare radiation-induced, organ-specific, secondary solid-tumor occurrence risks from conventional total body irradiation (TBI) and total marrow irradiation (TMI) for patients undergoing hematopoietic cell transplant. Methods and Materials We retrospectively selected 20 patients who received TMI treatments before hematopoietic cell transplant. Ten patients (5 men; 5 women) received 12 Gy to the skeletal bones, lymph nodes, and spleen, and the other 10 patients (5 men; 5 women) received an escalated dose of 20 Gy to the same targets and 12 Gy to the brain and liver. A conventional TBI treatment plan was generated for each patient with a prescription dose of 12 Gy, using anterior-posterior and posterior-anterior photon beams with lung shielding and a chest wall boost with electron beams. Secondary cancer risks were estimated using linear-exponential and plateau models for major organs. Results At the 12 Gy dose level, using the linear-exponential model, the total radiation-induced secondary solid-tumor risks for major organs were 159.3 ± 8.7 for men and 221.5 ± 14.4 for women per 10,000 people per year with the TMI plans, which is a reduction of 38.8% and 32.9%, respectively, compared with those with the TBI plans. At the 20 Gy dose level, the risks were 220.3 ± 8.3 for men and 298.5 ± 9.3 for women with the TMI plans, which is a reduction of 14.6% and 9.2%, respectively, compared with those with the 12 Gy TBI plans. Significant risk reductions were also found with the TMI plans using the plateau risk model. Conclusions At both the 12 Gy and 20 Gy prescription dose levels, a conditioning regimen using TMI could significantly lower overall radiation-induced secondary solid-tumor risks for major organs compared with a conditioning regimen with standard 12 Gy TBI. Clinical data from long-term follow-up studies are needed to verify the model predictions.

PURPOSE: To compare the effectiveness of different types of pharmacological agents to reduce organ specific edema following cardiopulmonary bypass (CPB).METHODS: Pubmed, Embase.com and Cochrane were searched for studies administrating a pharmacological agent before CPB. Primary outcome was postoperative edema.RESULTS: Forty-four studies (clinical n = 6, preclinical n = 38) fulfilled eligibility criteria. Steroids were used in most clinical studies (n = 5, 83%) and reduced postoperative edema in 4 studies, however heterogeneity precluded meta-analysis. In preclinical studies, a total of 31 different drugs were tested of which 20 (65%) reduced edema in at least one organ. Particularly neutrophil inhibitors, and modulators of coagulation or endothelial barrier reduced pulmonary edema (SMD -2.77 [-3.93, -1.61]; -1.29 [-2.12, -0.46], -2.33 [-4.69, 0.03], respectively) compared to no treatment. Reducing renal (SMD -0.91 [CI -1.65 to -0.18]), intestinal (SMD -1.98 [CI -3.92 to -0.04]) or myocardial (SMD -1.95 [CI -3.91 to -0.01]) edema following CPB required specific modulators of endothelial barrier.CONCLUSION: Overall, neutrophil inhibitors and direct modulators of endothelial barrier (PAR1, Tie2 signaling) most effectively reduced edema following CPB, in particular pulmonary edema. Future research should focus on a combination of these strategies to reduce edema and assess the effect on organ function and outcome following CPB.

We investigated whether different specialized organs in field-grown sugarcane follow the same temporal rhythms in transcription. We assayed the transcriptomes of three organs during the day: leaf, a source organ; internodes 1 and 2, sink organs focused on cell division and elongation; and internode 5, a sink organ focused on sucrose storage. The leaf had twice as many rhythmic transcripts (>68%) as internodes, and the rhythmic transcriptomes of the two internodes were more similar to each other than to those of the leaves. More transcripts were rhythmic under field conditions than under circadian conditions and most of their peaks were during the day. Among the transcripts that were considered expressed in all three organs, only 7.4% showed the same rhythmic time course pattern. The central oscillators of these three organs — the networks that generate circadian rhythms — had similar dynamics with different amplitudes. The differences between the rhythmic transcriptomes in circadian conditions and field conditions highlight the importance of field experiments to understand the plant circadian clock in natura. The highly specialized nature of the rhythmic transcriptomes in sugarcane organs probably arises from amplitude differences in tissue-specific circadian clocks and different sensitivities to environmental cues.One sentence summaryThe rhythmic transcriptome of field-grown sugarcane is highly organ-specific.

Safety related drug failures continue to be a challenge for pharmaceutical companies despite the numerous complex and lengthy in vitro assays and in vivo studies that make up the typical safety screening funnel. A lack of complete translation of animal data to humans can explain some of those shortcomings. Differences in sensitivity and drug disposition between animals and humans may also play a role. Many gaps exist for potential target tissues of drugs that cannot be adequately modeled in vitro. Microphysiological systems (MPS) may help to better model these target tissues and provide an opportunity to better assess some aspects of human safety prior to clinical studies. There is hope that these systems can supplement current preclinical drug safety and disposition evaluations, filling gaps and enhancing our ability to predict and understand human relevant toxicities. The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) MPS Affiliate is a group of pharmaceutical industry scientists who seek to expedite appropriate characterization and incorporation of MPS to potentially improve drug safety assessment and provide safer and more effective medicines to patients. In keeping with this mission, the IQ MPS Affiliate scientists have prepared a series of organotypic manuscripts for several key drug safety and disposition target tissues (lung, liver, kidney, skin, gastrointestinal, cardiovascular, and blood brain barrier/central nervous system). The goal of these manuscripts is to provide key information related to likely initial contexts of use (CoU) and key characterization data needed for incorporation of MPS in pharmaceutical safety screening including a list of characteristic functions, cell types, toxicities, and test agents (representing major mechanisms of toxicity) that can be used by MPS developers. Additional manuscripts focusing on testing biologically based therapeutics and ADME considerations have been prepared as part of this effort. These manuscripts focus on general needs for assessing biologics and ADME endpoints and include similar information to the tissue specific manuscripts where appropriate. The current manuscript is an introduction to several general concepts related to pharmaceutical industry needs with regard to MPS application and other MPS concepts that apply across the organ specific manuscripts.

Organ specific proteins (OSPs) possess great medical potentials both in clinics and in biomedical research. Applications of them — such as alanine transaminase, aspartate transaminase, and troponins — in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human population are well known, yet their effects on OSPs are less addressed. Here we use mouse as a model and implemented a scheme of breadth study to examine the pan-organ proteome for potential variations of organ specificity in different genetic backgrounds. Using reasonable resources, we generated pan-organ proteomes of four in-bred mouse strains. The results revealed a large diversity that is more profound among OSPs than the overall proteomes. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ specific that are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

Basically, mud therapy is a simple and effective treatment of several disorders of neurological, rheumatologically, cardiovascular, gynecological and inflammatory origin...

Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions.

Morphogenesis is an emergent property of biochemical and cellular interactions during development. Genome size and the correlated trait of cell size can influence these interactions through its effects on developmental rate and tissue geometry, ultimately driving the evolution of morphology. We tested the effects of genome size and body size evolution on heart and liver morphology using nine species of the salamander genus Plethodon (genome sizes 29.3–67 Gb). Our results show that whole organ size is determined by body size, whereas tissue structure changes dramatically with evolutionary increases in genome size. In the heart, increased genome size is correlated with a reduction of myocardia in the ventricle, yielding proportionally less force–producing mass and more empty space. In the liver, increased genome size is correlated with fewer and larger vascular structures, positioning hepatocytes farther from the circulatory vessels that transport key metabolites. Although these structural changes should have obvious impacts on organ function, their effects on organismal performance and fitness are likely negligible because low metabolic rates in salamanders relax selective pressure on key metabolic organ performance. Overall, this study reveals the effects of large genome and cell size on the developmental systems producing the heart and liver.

The relation between non-organ specific autoantibodies (NOSA) and hepatitis C virus (HCV) infection has been investigated within different communities resulting in different prevalence rates and patterns. The purpose of this study was to investigate the prevalence of some NOSA such as RF-IgG, ANA, ASMA, and LKM-1 in Egyptian patients with HCV group as compared with Egyptian healthy controls group. A total of 186 HCV positive serum samples in addition to 81 samples from healthy control were screened for the presence of some common autoantibodies (RF-IgG, ANA, ASMA, and LKM-1) using ELISA technique for ANA, ASMA, and LK-1 while RF-IgG was assayed by latex agglutination technique. The presence of these autoantibodies was tested in relation to some demographic variables and viral titers. Associations were assessed using logistic regression analysis adjusted for potential confounders. Among patients, 100 (53.7%) of 186 and 6 (7.4%) of 81 healthy control group were positive for at least one autoantibody. Furthermore, 2 patients (1%) were positive for three autoantibodies, whereas 22 patients (11.7%) were positive for 2 autoantibodies. The most prevalent autoantibody in anti-HCV-positive group was RF-IgG (87, 46.7%) followed by ASMA (26, 14%). The frequency of autoantibodies was bit higher in women as compared to men. Taken together, this study reports a non-significant difference in prevalence of NOSA between patients with HCV infection and healthy individuals except for ASMA. Likewise, no significant difference was found in prevalence of such autoantibodies when correlated with some demographic variables.

ÖZETAmaç: Bu çalışmada Türk toplumunda 0-15 yaş arası çocuklarda karaciğer, böbrekler ve dalak standart boyutlarının ultrasonografik olarak yaş, cinsiyet, boy ve kiloya göre hesaplanması amaçlandı. Gereç ve Yöntem: Çalışma için sistematik veya organospesifik hastalığı olmayan 302 sağlıklı çocuğun karaciğer için sağ lob organ derinliği, böbrekler için longütudinal uzunluk, genişlik ve hilus-korteks derinliği, dalak için poller arası maksimum uzunluk ve hilus düzeyinde maksimum genişlik ölçümleri yapıldı. Ayrıca çocukların yaş, cinsiyet, boy ve kilo değerleri kaydedildi. Bulgular: Karaciğer derinliği ortalamasının 100,49±18.46, sağ böbrek longitudinal uzunluğu ortalamasının 80.04 ±14.33, sol böbrek longitudinal uzunluğu ortalamasının 81.22±14.92, dalak longitudinal uzunluğu ortalamasının ise 81.24±15.51 olduğu gözlendi. Bulunan değerler ile somatik morfometrik parametreler (boy, kilo) ve yaş arasındaki lineer korelasyon değerleri anlamlı bulundu. Ölçülen her bir parametre için iki cinsiyet arasında anlamlı fark saptanmadı. Sonuç: Karaciğer, dalak ve böbrek boyutlarının yaşa, boy ve kiloya bağlı değiştiği normal değerlerin bu özelliklere göre modifiye edilmesi gerektiği görüldü. Her yaş grubunda Türk çocuklarda normal sınırlardaki değerler literatürde yer alan çalışmalarla büyük oranda benzerlik gösteriyordu.

Early detection of postoperative recurrence is beneficial for patients with cancer; however, optimal surveillance remains an issue. To optimize the follow-up plan, the estimation of an individual patient's risk of recurrence is indispensable.This study aimed to establish a statistical model for predicting the risk of organ-specific recurrence after curative resection of colon cancer.This was a retrospective cohort study at a tertiary referral hospital.This study included 1720 patients with colon cancer treated at the University of Tokyo Hospital between 1997 and 2015. Data were retrospectively retrieved from patient medical charts. The risk score was developed using a competing risk model in a derivation cohort (973 patients treated in 1997-2009) and then validated in a validation cohort (747 patients treated in 2010-2015).Patients who underwent curative resection for stage I to III colon cancer were included.The prediction of the incidence of postoperative liver and lung metastasis of colon cancer was measured.The factors selected for the prediction model for liver metastasis included differentiation, T category, venous invasion, N category, and preoperative CEA level. The model for lung metastasis included sex, lymphatic invasion, venous invasion, N category, preoperative CEA level, and malignant bowel obstruction. During external validation, the area under the curve at 60 months was 0.78 (95% CI, 0.71-0.84) for liver metastasis and 0.72 (95% CI, 0.64-0.81) for lung metastasis.The generalizability of the model to different healthcare settings remains to be elucidated.We developed a prediction model to estimate the risk of recurrence in the liver and lung after curative resection of colon cancer, which demonstrated good discrimination ability in the external validation cohort. Our model can aid clinicians and patients in customizing postoperative surveillance according to an individual patient's risk of organ-specific recurrence. See Video Abstract at http://links.lww.com/DCR/A977. DESARROLLO Y VALIDACIÓN DE UN MODELO DE PREDICCIÓN PARA RECURRENCIAS ESPECÍFICAS DESPUÉS DE RESECCIÓN CURATIVA DE UN CÁNCER DE COLON: La detección temprana de una recidiva postoperatoria es beneficiosa para los pacientes afectados de cáncer. Sin embargo, la mejor vigilancia sigue siendo un problema. Para optimizar el plan de seguimiento, la estimación del riesgo individual de recurrencia de un paciente es indispensable.Establecer un modelo estadístico para predecir el riesgo de recurrencia en un organo específico luego de la resección curativa de un cáncer de colon. DISEÑO:: Estudio retrospectivo de cohortes en un hospital de referencia terciaria.Este estudio incluyó 1720 pacientes con cáncer de colon tratados en el Hospital de la Universidad de Tokio entre 1997 y 2015. Los datos se recuperaron retrospectivamente de las historias clinicas de los pacientes. La puntuación de riesgo fué desarrollada utilizando un modelo de riesgo competitivo en cohortes de derivación (973 pacientes tratados en 1997-2009) y luego se lo validó en cohortes de validación (747 pacientes tratados en 2010-2015).Todos aquellos casos que se sometieron a una resección curativa de cáncer de colon en estadio I-III RESULTADOS PRINCIPLES:: La predicción de la incidencia de metástasis hepáticas y pulmonares postoperatorias del cáncer de colon.Los factores seleccionados para el modelo de predicción de metástasis hepáticas incluyeron diferenciación tumoral, categoría T, invasión venosa, categoría N y nivel de antígeno carcinoembrionario preoperatorio. El modelo de predicción de metástasis pulmonar incluyó el sexo del paciente, la invasión linfática, la invasión venosa, la categoría N, el nivel de antígeno carcinoembrionario preoperatorio y la obstrucción intestinal maligna. Durante la validación externa, el área inferior de la curva a 60 meses fue de 0,78 (intervalo de confianza del 95%: 0,71 a 0,84) para las metástasis hepáticas y de 0,72 (intervalo de confianza del 95%: 0,64 a 0,81) para las metástasis pulmonares.La generalización del presente modelo a diferentes entornos de atención en salud aún no ha podido ser dilucidado.Desarrollamos un modelo de predicción para estimar el riesgo de recurrencia en el hígado y el pulmón después de resección curativa de cáncer de colon, éste modelo demostró una buena capacidad de discriminación en las cohortes de validación externa. El modelo puede ayudar a médicos y pacientes a personalizar la vigilancia postoperatoria de acuerdo con el riesgo individual de recurrencia específica en un órgano específico. Vea el Resumen del Video en http://links.lww.com/DCR/A977.

Despite the recognition of the lethality of cancer metastasis and the importance of developing specific anti-metastasis therapies directed at the cancer metastatic cascade, the dynamics of cancer metastasis remains poorly understood. In this study, we examined the dynamics of circulating tumor cell (CTC) survival in the bloodstream using experimental mouse models. CTCs were arrested in the capillaries by adhesion to vascular endothelium within a few minutes after injection into the bloodstream. The loss of CTCs from the circulation followed a bi-phasic decay pattern, with the number of CTCs in the bloodstream being closely associated with the number of blood circulation cycles. The calculated in vivo Vd (apparent volume of distribution) of the CTC revealed organ specific binding of the CTCs. Moreover, confocal microscopy, in vivo fluorescence imaging in syngeneic mouse metastatic models and analysis of blood circulation patterns support the notion of organ-specific tumor metastasis. The present study suggests that organ-specific tumor metastasis is influenced by cooperation between blood circulation patterns and 'seed-soil' compatibility factors. These new findings provide further insights for optimized cancer metastatic prevention strategies such as by creating a hostile circulation microenvironment and targeting the organ-specific 'seed-soil' compatibility factors.

Tissue engineering (TE) is an emerging field where alternate/artificial tissues or organ substitutes are implanted to mimic the functionality of damaged or injured tissues. Earlier efforts were made to develop natural, synthetic, or semisynthetic materials for skin equivalents to treat burns or skin wounds. Nowadays, many more tissues like bone, cardiac, cartilage, heart, liver, cornea, blood vessels, and so forth are being engineered using 3-D biomaterial constructs or scaffolds that could deliver active molecules such as peptides or growth factors. Nanomaterials (NMs) due to their unique mechanical, electrical, and optical properties possess significant opportunities in TE applications. Traditional TE scaffolds were based on hydrolytically degradable macroporous materials, whereas current approaches emphasize on controlling cell behaviors and tissue formation by nano-scale topography that closely mimics the natural extracellular matrix. This review article gives a comprehensive outlook of different organ specific NMs which are being used for diversified TE applications. Varieties of NMs are known to serve as biological alternatives to repair or replace a portion or whole of the nonfunctional or damaged tissue. NMs may promote greater amounts of specific interactions stimulated at the cellular level, ultimately leading to more efficient new tissue formation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2433-2449, 2019.

Aging is a complex multidimensional process of progressive decline affecting multiple organ systems by a number of processes that are still not well understood. While many studies have focused on the approach of studying aging across multiple organs, assessment of the contribution of individual organs to overall aging processes is under appreciated. The ability to study and compare organs in the context of organismal aging has been documented recently using a geropathology grading platform in laboratory mice. This concept consists of identifying and grading age-related histologic lesions within organs to generate a quantitative lesion score for each organ, which is representative of the presence and degree of organ-related pathology, and can be compared to scores from other organs examined. This geropathology approach provides a powerful tool to elucidate the basic mechanisms of aging in multiple organs, as well as the response of organs to therapeutic interventions. Furthermore, ongoing work with the concept has expanded and adapted the geropathology grading system to other preclinical animal model species that are commonly used to understand disease associated phenotypes in aging humans, ultimately adding to the utility of the concept.