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Background: Amniotic fluid index (AFI) is a key element in fetal biophysical profile that predicts pregnancy outcome especially near term in primigravidae. The objective of the study was to determine a reference range of AFI in primigravidae of a local population having gestational age from 37 to 42 weeks. Methodology: This study was carried out from January 2019 to December 2019 after approval from Institutional Review Board and Ethical Committee at Shifa International hospital, Islamabad, Pakistan. Applying inclusion and exclusion criteria, a sample of 272 was selected. AFI was calculated for each subject using ultrasound and recorded on a data collection sheet. For the sake of simplicity and clinical relevance, the population was further stratified as term pregnancy (gestational age 37-39 weeks) and postdates pregnancy (40-42 weeks). The reference range of AFI was then calculated using mean ±two standard deviations. Results: The reference range of AFI for gestational age of 37-42 weeks (population as a whole) was 6.8- 17.2 cm. For term pregnancy, it was 7.5- 17.5 cm, and for postdate pregnancy, it was 5.8 to 15.4 cm. Conclusion: The reference range of AFI for gestational age of 37 to 42 weeks in Primigravida women was 6.8 to 17.2 cm. There is a decreasing trend in AFI as pregnancy advances from term to postdate. Keywords: Amniotic Fluid Index, Gestational age, Primigravida, Reference Range.

To screen and validate novel stool protein biomarkers of colorectal cancer (CRC). A novel aptamer-based screen of 1317 proteins was used to uncover elevated proteins in the stool of patients with CRC, as compared to healthy controls (HCs) in a discovery cohort. Selected biomarker candidates from the discovery cohort were ELISA validated in three independent cross-sectional cohorts comprises 76 CRC patients, 15 adenoma patients, and 63 healthy controls, from two different ethnicities. The expression of the potential stool biomarkers within CRC tissue was evaluated using single-cell RNA-seq datasets. A total of 92 proteins were significantly elevated in CRC samples as compared to HCs in the discovery cohort. Among Caucasians, the 5 most discriminatory proteins among the 16 selected proteins, ordered by their ability to distinguish CRC from adenoma and healthy controls, were MMP9, haptoglobin, myeloperoxidase, fibrinogen, and adiponectin. Except myeloperoxidase, the others were significantly associated with depth of tumor invasion. The 8 stool proteins with the highest AUC values were also discriminatory in a second cohort of Indian CRC patients. Several of the stool biomarkers elevated in CRC were also expressed within CRC tissue, based on the single-cell RNA-seq analysis. Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising CRC stool biomarkers, outperforming stool Hemoglobin. Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of CRC.

ObjectiveThe goal of these studies is to discover novel urinary biomarkers of lupus nephritis (LN).MethodsUrine from systemic lupus erythematosus (SLE) patients was interrogated for 1000 proteins using a novel, quantitative planar protein microarray. Hits were validated in an independent SLE cohort with inactive, active non-renal (ANR) and active renal (AR) patients, in a cohort with concurrent renal biopsies, and in a longitudinal cohort. Single-cell renal RNA sequencing data from LN kidneys were examined to deduce the cellular origin of each biomarker.ResultsScreening of 1000 proteins revealed 64 proteins to be significantly elevated in SLE urine, of which 17 were ELISA validated in independent cohorts. Urine Angptl4 (area under the curve (AUC)=0.96), L-selectin (AUC=0.86), TPP1 (AUC=0.84), transforming growth factor-β1 (TGFβ1) (AUC=0.78), thrombospondin-1 (AUC=0.73), FOLR2 (AUC=0.72), platelet-derived growth factor receptor-β (AUC=0.67) and PRX2 (AUC=0.65) distinguished AR from ANR SLE, outperforming anti-dsDNA, C3 and C4, in terms of specificity, sensitivity and positive predictive value. In multivariate regression analysis, urine Angptl4, L-selectin, TPP1 and TGFβ1 were highly associated with disease activity, even after correction for demographic variables. In SLE patients with serial follow-up, urine L-selectin (followed by urine Angptl4 and TGFβ1) were best at tracking concurrent or pending disease flares. Importantly, several proteins elevated in LN urine were also expressed within the kidneys in LN, either within resident renal cells or infiltrating immune cells, based on single-cell RNA sequencing analysis.ConclusionUnbiased planar array screening of 1000 proteins has led to the discovery of urine Angptl4, L-selectin and TGFβ1 as potential biomarker candidates for tracking disease activity in LN.

Inflammatory bowel disease (IBD) is an immune mediated chronic inflammation of the intestine, which can present in the form of Ulcerative Colitis (UC) or as Crohn's Disease (CD). Biomarkers are needed for reliable diagnosis and disease monitoring in IBD, especially in pediatric patients. Plasma samples from a pediatric IBD cohort were interrogated using an aptamer-based screen of 1322 proteins. The elevated biomarkers identified using the aptamer screen were further validated by ELISA using an independent cohort of 76 pediatric plasma samples, drawn from 30 CD, 30 UC, and 16 healthy controls (HC). Of the 1322 proteins screened in plasma from IBD patients, 129 proteins were significantly elevated when compared with healthy controls. Of these 15 proteins had a fold change (FC) greater than 2 and 28 proteins had a FC1.5. Neutrophil and extracellular vesicle signatures were detected among the elevated plasma biomarkers. When seven of these proteins were validated by ELISA, Resistin was the only protein that was significantly higher in both UC and CD (p0.01), with ROC AUC value of 0.82 and 0.77, respectively, and the only protein that exhibited high sensitivity and specificity for both CD and UC. The next most discriminatory plasma proteins were Elastase and Lactoferrin, particularly for UC, with ROC AUC values of 0.74 and 0.69, respectively. We have identified circulating Resistin, Elastase and Lactoferrin as potential plasma biomarkers of IBD in pediatric patients using two independent diagnostic platforms and two independent patient cohorts.

As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE cerebrospinal fluid (CSF) using an aptamer-based platform.CSF was obtained from NPSLE patients and subjected to proteomic assay using the aptamer-based screen. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison to other neurologic diseases.Forty proteins out of the 1,129 screened were found to be elevated in NPSLE CSF. Based on enzyme-linked immunosorbent assay validation, CSF levels of angiostatin, α2-macroglobulin, DAN, fibronectin, hepatocellular carcinoma clone 1, IgM, lipocalin 2, macrophage colony-stimulating factor (M-CSF), and serine protease inhibitor G1 were significantly elevated in a predominantly White NPSLE cohort (n = 24), compared to patients with other neurologic diseases (n = 54), with CSF IgM (area under the curve [AUC] 0.95) and M-CSF (AUC 0.91) being the most discriminatory proteins. In a second Hong Kong-based NPSLE cohort, CSF IgM (AUC 0.78) and lipocalin 2 (AUC 0.85) were the most discriminatory proteins. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF complement C3 was associated with an acute confusional state. Eleven molecules elevated in NPSLE CSF exhibited concordant elevation in the choroid plexus, suggesting shared origins.Lipocalin 2, M-CSF, IgM, and complement C3 emerge as promising CSF biomarkers of NPSLE with diagnostic potential.

In the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD., Stool biomarkers hold promise for monitoring disease activity and predicting clinical course in inflammatory bowel disease (IBD) as they originate from the inflamed tissue. Here the authors report an aptamer-based proteomic screen, and discover several stool proteins that predict remission at four weeks.

To screen and validate novel stool protein biomarkers of colorectal cancer (CRC).A novel aptamer-based screen of 1317 proteins was used to uncover elevated proteins in the stool of patients with CRC, as compared to healthy controls (HCs) in a discovery cohort. Selected biomarker candidates from the discovery cohort were ELISA validated in three independent cross-sectional cohorts comprises 76 CRC patients, 15 adenoma patients, and 63 healthy controls, from two different ethnicities. The expression of the potential stool biomarkers within CRC tissue was evaluated using single-cell RNA-seq datasets.A total of 92 proteins were significantly elevated in CRC samples as compared to HCs in the discovery cohort. Among Caucasians, the 5 most discriminatory proteins among the 16 selected proteins, ordered by their ability to distinguish CRC from adenoma and healthy controls, were MMP9, haptoglobin, myeloperoxidase, fibrinogen, and adiponectin. Except myeloperoxidase, the others were significantly associated with depth of tumor invasion. The 8 stool proteins with the highest AUC values were also discriminatory in a second cohort of Indian CRC patients. Several of the stool biomarkers elevated in CRC were also expressed within CRC tissue, based on the single-cell RNA-seq analysis.Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising CRC stool biomarkers, outperforming stool Hemoglobin. Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of CRC.

Epigallocatechin-3-gallate (EGCG) has been shown to attenuate obesity, fatty liver disease, hepatic inflammation and lipid profiles. Here, we validate the efficacy of EGCG in a murine model of non-alcoholic fatty liver disease (NAFLD) and extend the mechanistic insights. NAFLD was induced in mice by a high-fat diet (HFD) with 30% fructose. EGCG was administered at a low dose (25 mg/kg/day, EGCG-25) or high dose (50 mg/kg/day, EGCG-50) for 8 weeks. In HFD-fed mice, EGCG attenuated body and liver weight by ~22% and 47%, respectively, accompanied by ~47% reduction in hepatic triglyceride (TG) accumulation and ~38% reduction in serum cholesterol, resonating well with previous reports in the literature. In EGCG-treated mice, the hepatic steatosis score and the non-alcoholic steatohepatitis activity score were both reduced by ~50% and ~57%, respectively, accompanied by improvements in hepatic inflammation grade. Liver enzymes were improved ~2–3-fold following EGCG treatment, recapitulating previous reports. Hepatic flow cytometry demonstrated that EGCG-fed mice had lower Ly6C+, MHCII+ and higher CD206+, CD23+ hepatic macrophage infiltration, indicating that EGCG impactedM1/M2 macrophage polarization. Our study further validates the salubrious effects of EGCG on NAFLD and sheds light on a novel mechanistic contribution of EGCG, namely hepatic M1-to-M2 macrophage polarization. These findings offer further support for the use of EGCG in human NAFLD.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes regions of ulceration within the interior of the colon. UC is estimated to afflict hundreds of thousands of people in the United States alone. In addition to traditional colonoscopy, ultrasonic techniques can detect colitis, but have limited spatial resolution, which frequently results in underdiagnoses. Nevertheless, clinical diagnosis of colitis is still generally performed via colonoscopy. Optical techniques such as confocal microscopy and optical coherence tomography (OCT) have been proposed to detect UC with higher resolution. However, UC can potentially alter tissue biomechanical properties, providing additional contrast for earlier and potentially more accurate detection. Although clinically available elastography techniques have been immensely useful, they do not have the resolution for imaging small tissues, such as in small mammalian disease models. However, OCT-based elastography, optical coherence elastography (OCE), is well-suited for imaging the biomechanical properties of small mammal colon tissue. METHODS: In this work, we induced elastic waves in ex vivo mouse colon tissue using a focused air-pulse. The elastic waves were detected using a phase-stabilized swept source OCE system, and the wave velocity was translated into stiffness. Measurements were taken at six positions for each sample to assess regional sample elasticity. Additional contrast between the control and diseased tissue was detected by analyzing the dispersion of the elastic wave and tissue optical properties obtained from the OCT structural image. RESULTS: The results show distinct differences (P

Background: In this study, we investigate the impact of epigallocatechin gallate (EGCG), the most abundant and potent catechin in green tea, on a mouse model of inflammatory bowel disease (IBD) and the underlying mechanisms of action. Methods: C57BL/6J mice were subjected to dextran sulfate sodium (DSS)-induced IBD-like disease and then randomly divided into three groups: Model group (MD), low-dose EGCG group (LE, 20 mg/kg/d), and high-dose EGCG group (HE, 50 mg/kg/d). DSS-induced clinical and macroscopic changes were monitored daily. Intestinal permeability was assessed by FITC-Dextran assay. Results: Both high- and low-dose EGCG treatment alleviated clinical manifestations including body weight loss and disease activity index (DAI) of DSS-induced colitis. The DAI score was significantly improved after two days of EGCG treatment. At the end of the study, the macroscopic severity score (MSS) of HE and LE treatment groups were 2.4 &plusmn, 1.2, and 2.2 &plusmn, 1.0, respectively, significantly lower than that of the controls (5.0 &plusmn, 2.1). EGCG treatment also prevented colon shortening, and improved intestinal permeability and histopathological changes. In addition, EGCG treatment attenuated colon inflammation by suppressing colonic levels of pro-inflammatory cytokines IL-6, MCP-1, and TNF-alpha, and inhibited CD3+ T cell and CD68+ macrophage infiltration. Conclusion: EGCG is effective in inflammatory colitis because it reduces cellular and molecular inflammation, and reduces intestinal permeability.

Sporadic Creutzfeldt–Jakob disease (sCJD) is a rare but fatal type of spongiform encephalopathy with unknown cause. Unfortunately, definitive diagnosis of this disease can only be done by examination of postmortem brain tissue. Presumptive diagnosis is done through a combination of clinical manifestations, radiology results, and cerebrospinal fluid (CSF) testing for CSF 14‐3‐3. Even with these guidelines, premortem diagnosis of sCJD can be unreliable with high rates of misdiagnosis. This calls for more reliable biomarkers of the disease, allowing for better diagnosis as well as understanding the pathogenesis of sCJD. This review compiles potential genetic, protein, biomolecular, and imaging biomarker studies for sCJD since 2010, highlighting the promise of proteins, cytokines, and composite biomarkers for improving the diagnosis as well as understanding the pathogenesis of this mysterious ailment.

Our recent study has implicated bradykinin (BK) signaling as being of pathogenic importance in lupus. This study aims to investigate the biomarker potential of BK peptides, BK and BK-des-arg-9, in lupus and other rheumatic autoimmune diseases. Sera from systemic lupus erythematosus (SLE) patients and healthy subjects were screened for BK and BK-des-arg-9 by liquid chromatography–mass spectrometry metabolomics. Serum from 6-mo-old C57BL/6 mice and three murine lupus strains were also screened for the two peptides by metabolomics. Given the promising initial screening results, validation of these two peptides was next conducted using multiple reaction monitoring in larger patient cohorts. In initial metabolomics screening, BK-des-arg-9 was 22-fold higher in SLE serum and 106-fold higher in mouse lupus serum compared with healthy controls. In validation assays using multiple reaction monitoring and quadrupole time-of-flight mass spectrometry, BK and BK-des-arg-9 showed significant elevations in SLE serum compared with controls (p < 0.0001; area under the curve = 0.79–0.88), with a similar but less pronounced increase being noted in rheumatoid arthritis serum. Interestingly, increased renal SLE disease activity index in lupus patients was associated with reduced circulating BK-des-arg-9, and the reasons for this remain to be explored. To sum, increased conversion of BK to the proinflammatory metabolite BK-des-arg-9 appears to be a common theme in systemic rheumatic diseases. Besides serving as an early marker for systemic autoimmunity, independent studies also show that this metabolic axis may also be a pathogenic driver and therapeutic target in lupus.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes regions of ulceration within the interior of the colon. UC is estimated to afflict hundreds of thousands of people in the United States alone. Ultrasonic techniques can detect colitis, but have limited spatial resolution, which frequently results in underdiagnoses. Nevertheless, clinical diagnosis of colitis is still generally performed via colonoscopy. Optical techniques such as confocal microscopy and optical coherence tomography (OCT) have been proposed as higher resolution alternative imaging modalities to detect colitis. Additionally, IBD can potentially alter tissue biomechanical properties, which cannot be quantified from structural imaging alone. Elastography is a potential method to assess colon biomechanical properties to provide additional contrast for distinguishing healthy and diseased colon tissue. In this work, we induced elastic waves in ex vivo mouse colon tissue using a focused air-pulse. The elastic waves were detected using a phase-stabilized swept source optical coherence elastography system, and the wave velocity was translated into stiffness. Measurements were taken at six random positions for each sample in order to assess regional sample elasticity. The results show distinct differences ($p \lt 0.05$) in the stiffness between healthy and IBD-diseased samples, with a Young's Modulus of $10.2 \pm 3.7$ kPa and $4.9 \pm 0.3$ kPa, respectively. Dispersion analysis presents another parameter to distinguish tissue health. The high frequency components of the phase velocity dispersion curve indicate a variation between healthy and IBD colonic tissue. Our results show that OCE may be useful for detecting IBD noninvasively.

Objective To obtain the comprehensive transcriptome profile of human citrulline-specific B cells from patients with rheumatoid arthritis (RA). Methods Citrulline- and hemagglutinin-specific B cells were sorted by flow cytometry using peptide-streptavidin conjugates from the peripheral blood of RA patients and healthy individuals. The transcriptome profile of the sorted cells was obtained by RNA-sequencing, and expression of key protein molecules was evaluated by aptamer-based SOMAscan assay and flow cytometry. The ability of these proteins to effect differentiation of osteoclasts and proliferation and migration of synoviocytes was examined by in vitro functional assays. Results Citrulline-specific B cells, in comparison to citrulline-negative B cells, from patients with RA differentially expressed the interleukin-15 receptor α (IL-15Rα) gene as well as genes related to protein citrullination and cyclic AMP signaling. In analyses of an independent cohort of cyclic citrullinated peptide-seropositive RA patients, the expression of IL-15Rα protein was enriched in citrulline-specific B cells from the patients' peripheral blood, and surprisingly, all B cells from RA patients were capable of producing the epidermal growth factor ligand amphiregulin (AREG). Production of AREG directly led to increased migration and proliferation of fibroblast-like synoviocytes, and, in combination with anti-citrullinated protein antibodies, led to the increased differentiation of osteoclasts. Conclusion To the best of our knowledge, this is the first study to document the whole transcriptome profile of autoreactive B cells in any autoimmune disease. These data identify several genes and pathways that may be targeted by repurposing several US Food and Drug Administration-approved drugs, and could serve as the foundation for the comparative assessment of B cell profiles in other autoimmune diseases.

In recent years, aptamers have come to replace antibodies in high throughput multiplexed experiments. The aptamer-based biomarker screening technology, which kicked off in 2010, is capable of interrogating thousands of proteins in a very small sample volume. With this new technology, researchers hope to find clinically appropriate biomarkers for a myriad of illnesses by screening human body fluids. In this work, we have reviewed a total of eight studies utilizing aptamer-based biomarker screens of human body fluids, and have highlighted novel protein biomarkers discovered.

Although the contribution of B-cell derived autoreactive antibodies to rheumatoid arthritis (RA) has been studied extensively, the autoantibody-independent roles of B cells in the progression of the disease is not well-defined. Here we present the first comprehensive transcriptome profile of human autoreactive B cells in an autoimmune disease by performing RNA-sequencing of citrulline-specific B cells from RA patients. In order to facilitate a comprehensive understanding of the profile of these citrulline-specific (RA-CCPPOS) B cells, we performed comparative analyses to both citrulline-negative (RA-CCPNEG) B cells from the same donors, and identified 431 differentially expressed genes (DEGs); and hemagglutinin-specific (HA) B cells from healthy individuals and identified 1658 DEGs. Three-way comparisons of these B cell populations demonstrated that RA-CCPPOS B cells, in comparison to the RA-CCPNEG B cells, demonstrate a potential role in protein citrullination and inflammation; RA-CCPPOS B cells in comparison to HA-specific B cells demonstrate RA-specific signatures like the expression of pro-inflammatory cytokines, chemokines, costimulatory molecules and B-cell activation cascades; and all B cells from RA patients demonstrated a significant impact of the multitude of TNF signaling pathways. Furthermore, transcription factor profiling suggested that cyclic AMP (cAMP) related pathways and downstream signaling molecules are selectively enriched in RA-CCPPOS cells in comparison to the other two B cell subsets. We advanced the understanding of the citrulline reactive B cells in RA pathophysiology by documenting and validating two novel observations in independent cohorts of patients: (1) the expression of IL15Rα is restricted to citrulline-specific cells within RA patients and the concentration of soluble IL15Rα is elevated in the sera of RA patients, (2) B cells from RA patients are capable of producing epidermal growth factor ligand, amphiregulin (AREG) which in turn has a direct impact on the mechanistic effectors of RA, osteoclasts and fibroblastlike synoviocytes (FLS). Overall, our comprehensive dataset identifies several existing FDA-approved drugs that can potentially be repurposed for RA and can serve as a foundation for studying the multi-faceted roles of B cells in other autoimmune diseases.

Background Lupus Nephritis (LN) affects close to half of all SLE patients and is currently diagnosed through kidney biopsy. In search for a noninvasive diagnostic method, four serum biomarkers of SLE (IGFBP2, sTNFRII, Axl, VCAM1) were valued for their diagnostic potential in the saliva of SLE patients. Methods IGFBP2, STNFRII, Axl, VCAM1 were ELISA assayed in the serum and saliva of SLE patients (16 inactive, 10 active non-renal, 10 active renal) and 14 healthy controls. Group wise analysis by Mann Whitney test and Spearman correlation analyses between serum and saliva were done. Results IGFBP2 was elevated in SLE serum compared to controls (FC=3.2 P=0.0002) while sTNFRII and VCAM1 showed elevation in active compared to inactive SLE (FC=2.2 P=0.002 and FC=2.8 P Conclusion Although all four biomarkers (IGFBP2, sTNFRII, Axl, VCAM1) have shown diagnostic potential in SLE serum, only IGFBP2 and sTNFRII were elevated in SLE saliva. Further exploration into other salivary biomarkers through an unbiased aptamer based protein screening platform is in progress.

Background Given the potential side effects associated with conventional medical treatment of Inflammatory Bowel Disease (IBD), dietary supplements have been investigated by several groups. We tested if epigallocatechin gallate (EGCG) may be beneficial in IBD. Methods 36 C57BL/6J mice were subjected to dextran sulfate sodium (DSS)-induced IBD and divided into 3 groups: model group (MD; no EGCG), low dose EGCG group (LE, 20 mg/kg/d) and high dose EGCG group (HE, 50 mg /kg/d). Results Both high and low dose EGCG treatment alleviated clinical manifestations of IBD including body weight loss and disease activity index (DAI): HE: 3.3 and LE: 2.8 vs. 8.3 in MD (p < 0.001, n=8–10 mice/group). Macroscopic severity score (MSS) of HE and LE groups were 2.4, and 2.2, respectively, significantly lower than in MD (5.0, P < 0.01). The mean colon length of MD group was 5.8 cm; treatment with EGCG restored colon length (HE: 6.5 cm; LE: 6.4 cm). Intestinal permeability was improved as demonstrated by FITC-Dextran assay (HE: 3.28; LE: 2.85, vs. MD group: 6.69 ng/ml, P < 0.001) .The colitis histology score of HE (1.54) and LE (0.42) groups were significantly lower than that in MD (4.3, P < 0.001). In addition, EGCG treatment reduced colonic levels of pro-inflammatory cytokines: IL-6 (HE: 0.45; LE group: 0.41 vs MD: 0.89 ng/g tissue, P =0.03), MCP-1 (HE: 1.83; LE: 1.87, vs MD: 3.5 ng/g tissue P = 0.01) and TNF-alpha (HE: 8.87; LE: 10 vs MD: 21.7 ng/g tissue, P Conclusion These results underscore the therapeutic potential of EGCG in the treatment of IBD, which appear to be mediated through multiple inflammatory pathways.

Background Here, we examine the therapeutic efficacy of Epigallocatechin-3-gallate, the most potent catechin in green tea, on nonalcoholic fatty liver disease (NAFLD), a growing epidemic in humans. Methods NAFLD was induced by high-fat diet (HFD) with 30% fructose in drinking water for 8 weeks. Mice were divided into 3 groups: model group (MD; no EGCG), low dose EGCG group (LE, 20 mg/kg/d) and high dose EGCG group (HE, 50 mg/kg/d). Liver histology, serum lipid prolife, liver function as well as liver M1/M2 polarization were evaluated. Results At the end of the experiment, the mean body weight of LE and HE mice were 39.7g and 45.7g, while it was 51.9g in the MD group (P< 0.05). Similarly, liver weights in the LE and HE groups (means = 1.44g, and 1.68g, respectively) were lower than that in MD (2.94g, P < 0.01). Liver dysfunction observed in the MD group (mean AST=133.2 U/L and ALT=183.4 U/L), was significantly improved in both LE (44.8 U/L, 86.8 U/L, respectively, P < 0.001) and HE groups (83.63 U/L, 117.6 U/L, respectively P < 0.05). Serum cholesterol, HDL, triglyceride levels were increased in the MD group, but lowered in both LE and HE mice (p Conclusion EGCG subdued NAFLD despite consumption of HDF and high fructose water, marked by improved liver function and serum lipid profile, as well as M1/M2 polarization. EGCG should be investigated as a therapeutic modality in human NAFLD.

Background Systemic Lupus Erythematous (SLE) is a chronic inflammatory autoimmune disease marked by flares in multiple organ systems. Leading causes of morbidity and mortality in this disease include lupus nephritis and renal failure. Because the diagnosis of lupus nephritis is currently done using kidney biopsy, noninvasive diagnostic biomarkers are crucially needed to limit the use of this costly and invasive procedure. In this effort, active renal SLE patients’ urine was interrogated for potential biomarkers using a novel quantitative antibody array based protein screen of 1000 protein targets. Methods The urine of 9 active renal (AR), 6 active non-renal (ANR) patients, and 9 healthy controls (HC) were subjected to a quantitative antibody based protein screen of 1000 unique human proteins. After creatinine normalization, dysregulated proteins were selected for further validation using group wise fold change (FC) and Mann Whitney tests. Results The quantitative array based screen of 1000 targets showed 336 proteins to be elevated in the urine of active SLE patients compared to HC. Of these, 8 proteins were elevated in the urine of AR patients compared to ANR (FC>2 P 0.6 in 60% of proteins validated thus far). Relationship of biomarkers to disease activity and renal pathology is under investigation. Conclusions We have successfully validated one of the largest targeted proteomic technologies currently available for biomarker identification. Although validation of hits as diagnostic biomarkers is still in progress, the identified proteins show promise in the noninvasive diagnosis of active renal disease in SLE patients.