BACKGROUND/AIMS: Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB). METHODS: Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1φ marker) and CD163/CD68 (an M2φ marker), and the ratio of M1φ to M2φ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment. RESULTS: M1φ polarization was more prominent in CD biopsies (P=0.002) than in iTB (P=0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1φ predominance was significant (P=0.001). In iTB, the densities of M1φ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1φ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients. CONCLUSIONS: Proinflammatory M1φ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD.
Biopsy ; Colon ; Crohn Disease* ; Granuloma ; Humans ; Immune System ; Immunohistochemistry ; Macrophage Activation ; Macrophages* ; Monocytes ; Mucous Membrane ; Pathology ; Phenotype ; Tuberculosis*

A titanium implant surface when coated with biodegradable, highly porous, osteogenic nanofibrous coating has shown enhanced intrinsic osteoinductive and osteoconductive properties. This coating mimics extracellular matrix resulting in differentiation of stem cells present in the peri-implant niche to osteoblast and hence results in enhanced osseointegration of the implant. The osteogenic nanofibrous coating (ONFC) consists of poly-caprolactone, gelatin, nano-sized hydroxyapatite, dexamethasone, ascorbic acid and beta-glycerophosphate. ONFC exhibits optimum mechanical properties to support mesenchymal stem cells and steer their osteogenic differentiation. ONFC was subjected to various characterization tests like scanning electron microscopy, Fourier-transform infrared spectroscopy, x-ray diffractometry, thermal degradation, biomineralization, mechanical properties, wettability and proliferation assay. In pre-clinical animal trials, the coated implant showed enhanced new bone formation when placed in the tibia of rabbit. This novel approach toward implant bone integration holds significant promise for its easy and economical coating thus marking the beginning of new era of electrospun osteogenic nanofibrous coated bone implants.
Animals ; Ascorbic Acid ; Dexamethasone ; Durapatite ; Extracellular Matrix ; Gelatin ; Mesenchymal Stromal Cells ; Microscopy, Electron, Scanning ; Osseointegration* ; Osteoblasts ; Osteogenesis ; Spectrum Analysis ; Stem Cells ; Tibia ; Titanium* ; Wettability

BACKGROUND/AIMS: Aberrant crypt foci (ACF) are early microscopic lesions of the colonic mucosa, which can be detected by magnified chromoendoscopy. Herein, we have investigated whether ACF identified in different clinical groups can be differentiated based on their characteristics. METHODS: Macroscopically unremarkable mucosal flaps were collected from 270 fresh colectomies and divided into 3 clinical groups: colorectal carcinoma (group A), disease controls having known pre-neoplastic potential (group Bc), and disease controls without risk of carcinoma development (group Bn). Topographic and histologic analysis, immunohistochemistry, and molecular studies (high-resolution melt curve analysis, real-time polymerase chain reaction, and Sanger sequencing) were conducted for certain neoplasia-associated markers. RESULTS: ACF were seen in 107 cases, out of which 72 were left colonic ACF and 35 right colonic ACF (67.2% vs. 32.7%, P=0.02). The overall density of left colonic ACF was 0.97/cm, which was greater than the right colonic ACF density of 0.81/cm. Hypercrinia was present in 41 out of 72 left colonic ACF and in 14 out of 35 right colonic ACF (P=0.01). Immunohistochemical expression of p53 was also greater in left colonic ACF than in right colonic ACF (60.5% vs. 38.2%, P=0.03). However, ACF identified among the 3 clinical groups did not show any distinguishing topographic, histological, or genetic changes. CONCLUSIONS: Left colonic ACF appear to be high-risk based on their morphological and prototypic tumor marker signature. ACF identified in different clinical groups do not show significant genotypic or topographic differences. Further detailed genetic studies are required to elucidate them further.
Aberrant Crypt Foci ; Colectomy ; Colon ; Colorectal Neoplasms ; Humans ; Immunohistochemistry ; Mucous Membrane ; Real-Time Polymerase Chain Reaction

BACKGROUND/AIMS: The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies. METHODS: We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists. RESULTS: Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%–85.03%) and interobserver (24.6%–71.5%) agreements. CONCLUSIONS: Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD.
Biopsy ; Celiac Disease ; Classification ; Cohort Studies ; Epithelial Cells ; Humans ; Intestine, Small ; Logistic Models ; Lymphocyte Count ; Observer Variation ; Sensitivity and Specificity

The phytoecdysteroids (PEs) comprise a large group of biologically-active plant steroids, which have structures similar to those of insect-molting hormones. PEs are distributed in plants as secondary metabolites that offer protection against phytophagus (plant-eating) insects. When insects consume the plants containing these chemicals, they promptly molt and undergo metabolic destruction; the insects eventually die. Chemically, ecdysteroids are a group of polyhydroxylated ketosteroids that are structurally similar to androgens. The carbon skeleton of ecdysteroids is termed as cyclopentanoperhydro-phenanthrene with a