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1.  Carriage prevalence of carbapenem-resistant Enterobacteriaceae in stool samples: A surveillance study 
Background
With more people being exposed to antibiotics, intestinal microflora faces constant pressure of antibiotic selection, which has resulted in the emergence of multidrug resistant strains. This may pose a severe problem as intestinal Enterobacteriaceae members are commonly implicated in human infections.
Aims
This surveillance study was undertaken to investigate the carriage of carbapenem-resistant Enterobacteriaceae (CRE) in the gastrointestinal tract among patients attending the outpatient clinic in a tertiary care center of East Delhi, India.
Method
We performed a prospective surveillance study to screen 242 Enterobacteriaceae isolates for carbapenemase production from the stool samples of 123 outpatients attending a tertiary care hospital in East Delhi over a four-month period.
Results
Twenty-four (9.9 per cent) isolates demonstrated carbapenemase activity among 242 screened Enterobacteriaceae isolates. Four stool samples had two isolates of different species, both eliciting this feature and therefore indicating presence of multiple carbapenem-resistant Enterobacteriaceae (CRE) isolates in a single sample.
Conclusion
Screening for carriage of CRE in stools of patients undergoing elective or emergency gastrointestinal surgical procedures, with haematological malignancies taking chemotherapy, or those planned for bone marrow transplantation can guide clinicians about gut colonisation of multidrug-resistant Enterobacteriaceae as these groups of patients are at risk of possible endogenous infection.
doi:10.4066/AMJ.2014.1926
PMCID: PMC3941578  PMID: 24611074
Carbapenem resistant Enterobacteriaceae; gut colonisation; prophylactic antibiotic
2.  MicroRNA let-7e is associated with the pathogenesis of experimental autoimmune encephalomyelitis 
European journal of immunology  2012;43(1):104-114.
MicroRNAs (miRNAs) play important roles in the regulation of immune responses. There is evidence that miRNAs also participate in the pathogenesis of multiple sclerosis (MS), but how the miRNAs regulate the pathogenesis of MS is still under investigation. The identification of new members of the miRNA family associated with the pathogenesis of MS could facilitate early diagnosis and treatment. Here we show that the level of miRNA let-7e is significantly upregulated in experimental autoimmune encephalomyelitis (EAE), an animal model of MS using miRNA array and quantitative real-time PCR. The expression of let-7e was mainly in CD4+ T cells and infiltrated mononuclear cells of central nervous system, and highly correlated with the development of EAE. We found that let-7e silencing in vivo inhibited encephalitogenic Th1 and Th17 cells and attenuated EAE, with reciprocal increase of Th2 cells; overexpression of let-7e enhanced Th1 and Th17 cells and aggravated EAE. We also identified IL-10 as one of the functional targets of let-7e. Together, we propose that let-7e is a new miRNA involved in the regulation of encephalitogenic T-cell differentiation and the pathogenesis of EAE.
doi:10.1002/eji.201242702
PMCID: PMC3650085  PMID: 23079871
MicroRNA; mir-let-7e; EAE/MS; Th1/Th2 cells; Cell differentiation
3.  Estimation of serum β2-microglobulin in potentially malignant disorders and squamous cell carcinoma of the oral cavity: A clinicopathological study 
Dental Research Journal  2014;11(1):109-113.
Background:
Tumor markers are substances, which quantitatively changes in serum, during the tumor development, one such tumor marker is serum β2-microglobulin (β2-m). The aim of this study was to establish the role of β2-m as a biochemical parameter for diagnosis and prognosis of oral carcinoma by estimation of serum β2-m levels in potentially malignant lesions, conditions, and oral squamous cell carcinoma.
Materials and Methods:
The study was carried out on 48 subjects (16 control, 8 oral submucous fibrosis, 8 oral leukoplakia, and 16 oral squamous cell carcinoma patients of different stages), conducted at department of Oral Medicine, Kothiwal Dental College, Moradabad, India. Under aseptic precautions, 5 ml venous blood was drawn and serum was separated. Estimation of β2-m level in serum was carried out by enzyme linked immunosorbent assay. The data were analyzed by using the statistical package for social sciences (SPSS 17.0) software. Cases and controls were tested for statistical significance with one-way ANOVA with post-hoc Tukey's HSD. Values of P < 0.05 were considered significant.
Results:
The mean serum β2-m level in the control group was 1.173 ± 0.059, in potentially malignant lesions/conditions group was 1.688 ± 0.137 and in oral squamous cell carcinoma group was 2.835 ± 0.0313. This progressive increase in serum β2-m level was found to be highly significant (P value < 0.001). Results of Receiver operating characteristic analysis showed β2-m as a 100% sensitive and specific biomarker for oral squamous cell carcinoma.
Conclusion:
The present study establishes β2-m as a specific biological tumor marker for diagnostic and prognostic evaluation of oral squamous cell carcinoma.
PMCID: PMC3955303
β2-microglobulin; enzyme linked immunosorbent assay; squamous cell carcinoma; tumor markers
4.  Training module for cheiloscopy and palatoscopy in forensic odontology 
Introduction:
Studies of lip prints and palatal rugae, dates back to late 19th and early 20th centuries and since then, various methods of classification and analysis were introduced, however systematic recording and analysis of data is still need to improve further, to arrive at flawless and meaningful conclusions. Moreover, the awareness among dental personnel regarding the practical knowledge of cheiloscopy and palatoscopy is ambiguous. So, efforts have been made to introduce training module to improve the education of cheiloscopy and palatoscopy for dental students.
Aims and Objective:
1. To prepare training module for cheiloscopy and palatoscopy. 2. To assess the efficacy of designed training module.
Materials and Methods:
Training module was used to train the dental students. Random matching of lip and palatal rugae patterns was carried out by dental students before and after training. Pre- and post-training matched results were then compared. Intraobserver variability assessed by comparing first and second assessment of lip print and palatal rugae patterns.
Results:
It was inferred statistically that training module had improved the ability to identify individuals based on lip prints and palatal rugae, with insignificant intraobserver variation.
doi:10.4103/0975-1475.127768
PMCID: PMC3970386
Lip print; palatal rugae; training module
5.  The Severity of Experimental Autoimmune Cystitis Can be Ameliorated by Anti-CXCL10 Ab Treatment 
PLoS ONE  2013;8(11):e79751.
Background
Interstitial cystitis (IC), more recently called painful bladder syndrome (PBS) is a complex disease associated with chronic bladder inflammation that primarily affects women. Its symptoms include frequent urinary urgency accompanied by discomfort or pain in the bladder and lower abdomen. In the United States, eight million people, mostly women, have IC/PBS. New evidence that autoimmune mechanisms are important in the pathogenesis of IC/PBS triggered interest.
Methodology/Principal Findings
SWXJ mice immunized with a homogenate of similar mice’s urinary bladders develop an autoimmune phenotype comparable to clinical IC with functional and histological alterations confined to the urinary bladder. Using the murine model of experimental autoimmune cystitis (EAC), we found that serum levels of CXCR3 ligand and local T helper type 1 (Th1) cytokine are elevated. Also, IFN-γ-inducible protein10 (CXCL10) blockade attenuated overall cystitis severity scores; reversed the development of IC; decreased local production of CXCR3 and its ligands, IFN-γ, and tumor necrosis factor-α (TNF-α); and lowered systemic levels of CXCR3 ligands. Urinary bladder CD4+ T cells, mast cells, and neutrophils infiltrates were reduced following anti-CXCL10 antibody (Ab) treatment of mice. Anti-CXCL10 Ab treatment also reversed the upregulated level of CXCR3 ligand mRNA at urinary bladder sites. The decreased number and percentage of systemic CD4+ T cells in EAC mice returned to normal after anti-CXCL10 Ab treatment.
Conclusion/Significance
Taken together, our findings provide important new information about the mechanisms underlying EAC pathogenesis, which has symptoms similar to those of IC/PBS. CXCL10 has the potential for use in developing new therapy for IC/PBS.
doi:10.1371/journal.pone.0079751
PMCID: PMC3836899  PMID: 24278169
6.  Minor salivary glands and dental caries: Approach towards a new horizon 
Introduction:
Reduction of functioning minor salivary glands may contribute to emergence of mucosal infections, mucosal ulceration, and possibly dental caries. A study was, therefore, designed to understand the exact role of minor salivary gland secretions over dental caries.
Methodology:
We studied the average labial distribution of functional minor salivary glands using various pre-defined locations, counted the minor salivary gland secretion imprints, and correlated the decayed missing filledlevels in subjects. The functional level and amount of secretion of minor salivary gland were evaluated. The radial immunodiffusion was performed by Diffu-Plate kit and the dimensions of the ring were correlated with the amount of immunoglobulin A in saliva.
Results:
The mean number of functional labial minor salivary glands, amount of secretion, level of glycoprotein secretion, and immunoglobulin A secretion levels could very well dictate the functional status and role of minor salivary glands over caries assessment.
Conclusion:
The above-mentioned tests could be of major significance in routine diagnosis of the most common oral disease, i.e., dental caries.
doi:10.4103/0976-9668.117000
PMCID: PMC3783781  PMID: 24082733
Radial immunodiffusion; salivary immunoglobulin A; unstimulated whole saliva
7.  Effect of rate-adaptive pacing on performance and physiological parameters during activities of daily living in the elderly: results from the CLEAR (Cylos Responds with Physiologic Rate Changes during Daily Activities) study 
Europace  2013;15(6):849-856.
Aims
For most elderly pacemaker patients, evaluation of rate-adaptive pacing using treadmill and bicycle tests is impractical and not representative of typical daily activities. This study was designed to compare the performance and physiological response of the closed-loop stimulation (CLS) rate-adaptive sensor to accelerometer (XL) and no rate sensor (DDD) during typical daily activity testing.
Methods and results
Subjects recently implanted with a Cylos pacemaker completed timed activities of daily life testing, which included walking, sweeping, and standing from a seated position. Activity performance and physiological response from each sensor mode was evaluated for subjects requiring ≥80% pacing. Overall, 74 subjects needed ≥80% pacing during at least one test. An increase in the area swept (CLS vs. XL, 1.67 m2 difference, P = 0.009; CLS vs. DDD, 1.59 m2 difference, P = 0.025) and a decrease in the prevalence of orthostatic hypotension (OH) after standing 1 min (CLS vs. XL, odds ratio = 0.16, P = 0.006; CLS vs. DDD, odds ratio = 0.18, P = 0.012) was observed in the CLS mode as compared with XL and DDD. No statistical difference in walk distance was observed between CLS and XL or CLS and DDD.
Conclusion
In acute testing, as compared with XL and DDD, CLS provides a more physiological response during the performance of activities of daily living for subjects with ≥80% pacing. This is clinically reflected in better performance during the sweep test as well as a decrease in the prevalence of OH in our elderly population.
Clinicaltrials.gov identifier: NCT00355797
doi:10.1093/europace/eus425
PMCID: PMC3663333  PMID: 23419655
Rate-adaptive pacing; Closed-loop stimulation; Accelerometer; Orthostatic hypotension
8.  Role of resveratrol-induced CD11b+ Gr-1+ myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3+ T cells and amelioration of chronic colitis in IL-10−/− mice 
Brain, behavior, and immunity  2011;26(1):72-82.
Resveratrol, a naturally occurring polyphenol has received significant attention as a potent anti-inflammatory agent. Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Myeloid derived suppressor cells (MDSCs) are a heterogeneous population characterized by the co-expression of CD11b+ and Gr-1+ and have long been known for their immunosuppressive function. We report that resveratrol effectively attenuated overall clinical scores as well as various pathological markers of colitis in IL-10−/− mice by down regulating Th1 responses. Resveratrol lessened the colitis-associated decrease in body weight and increased levels of serum amyloid A (SAA), CXCL10 and colon TNF-α, IL-6, RANTES, IL-12 and IL-1β concentrations. After resveratrol treatment, the percentage of CXCR3 expressing T cells was decreased in the spleen, mesenteric lymph nodes (MLN), and intestinal lamina propria (LP). However, the percentage and absolute numbers of CD11b+ and Gr-1+cells in the lamina propria (LP) and spleen were increased after resveratrol treatment as compared with the vehicle treatment. Co-culture of resveratrol induced CD11b+ Gr-1+ cells with T cells, attenuated T cell proliferation, and most importantly reduced IFN-γ and GM-CSF production by LP derived T cells from vehicle treated IL-10−/− mice with chronic colitis. The current study suggests that administration of resveratrol into IL-10−/− mice induces immunosuppressive CD11b+ Gr-1+ MDSCs in the colon, which correlates with reversal of established chronic colitis, and down regulation of mucosal and systemic CXCR3+ expressing effector T cells as well as inflammatory cytokines in the colon. The induction of immunosuppressive CD11b+ Gr-1+ cells by resveratrol during colitis is unique, and suggests an as-yet-unidentified mode of anti-inflammatory action of this plant polyphenol.
doi:10.1016/j.bbi.2011.07.236
PMCID: PMC3506001  PMID: 21807089
Inflammation; Resveratrol; Colitis; CXCR3; CD11b+ and Gr-1+ and MDSCs
10.  Revealing anti-cariogenic efficacy of smokeless tobacco: A pilot study 
Background:
The tobacco plant, Nicotiana tabacum, has been responsible for more deaths than any other herb. However, the literature has also been endowed with its use as “holy herb” since the pre-Columbian era. Used for treating pain, poisonous bites, ulcers, nasal polyps, and basal cell carcinoma; it also acts as an important ingredient of commercially available toothpastes; and even used as tobacco vaccines against Streptococcus species as highlighted in the literature.
Aims and Objectives:
(1) To elicit the anti-microbial property of tobacco against Streptococcus mutans, if any, in raw smokeless tobacco. (2) To study the relationship of duration and growth inhibition efficacy of smokeless tobacco.
Materials and Methods:
Extracts were prepared by centrifugation of mixed raw smokeless tobacco with Ringer's lactate solution and with saliva. The extracts were placed in wells prepared on Mitis salivarius culture plate and incubated at 37°C for 24 h after 0 h, 1 h, and 2 h of extract preparation. The inhibition zones were measured on the underside of plate using the vernier calipers.
Results:
Smokeless tobacco has a statistically significant zone of inhibition, which proves its anti-microbial activity against S. mutans. However, the mean zones of inhibition were greater for Ringer's lactate and tobacco group as compared to test samples (saliva and tobacco) with subsequent reduction of inhibition zones with an increase in duration.
Conclusion:
The anti-microbial property of extensive tobacco resources can be utilized from their extracts in order to balance the deterioration it had caused to mankind.
doi:10.4103/0973-029X.110727
PMCID: PMC3687190  PMID: 23798831
Anti-cariogenecity; Streptococcus mutans;  tobacco
11.  Resveratrol (trans-3,5,4'-trihydroxystilbene) suppresses EL4 tumor growth by induction of apoptosis involving reciprocal regulation of SIRT1 and NF-κB 
Molecular nutrition & food research  2011;55(8):1207-1218.
Scope
Understanding the molecular mechanisms through which natural products and dietary supplements exhibit anticancer properties is crucial and can lead to drug discovery and chemoprevention. The current study sheds new light on the mode of action of Resveratarol (RES), a plant-derived polyphenolic compound, against EL-4 lymphoma growth.
Methods and results
Immuno-compromised NOD/SCID mice injected with EL-4 tumor cells and treated with RES (100 mg/kg body weight) showed delayed development and progression of tumor growth and increased mean survival time. RES caused apoptosis in EL4 cells through activation of aryl hydrocarbon receptor (AhR) and upregulation of Fas and FasL expression in vitro. Blocking of RES-induced apoptosis in EL4 cells by FasL mAb, cleavage of caspases and PARP, and release of cytochorme c, demonstrated the participation of both extrinsic and intrinsic pathways of apoptosis. RES also induced upregulation of SIRT1 and downregulation of NF-kB in EL4 cells. SiRNA-mediated down regulation of SIRT1 in EL4 cells increased the activation of NF-kB but decreased RES-mediated apoptosis, indicating the critical role of SIRT1 in apoptosis via blocking activation of NF-kB.
Conclusion
These data suggest that RES-induced SIRT1 upregulation promotes tumor cell apoptosis through negative regulation of NF-kB, leading to suppression of tumor growth.
doi:10.1002/mnfr.201000576
PMCID: PMC3516994  PMID: 21520490
Cancer; Lymphoma; Resveratrol; AhR; Fas; FasL; Apoptosis; Extrinsic pathway; Intrinsic pathway
12.  Distribution of Aedes albopictus (Diptera, Culicidae) in southwestern Pacific countries, with a first report from the Kingdom of Tonga 
Parasites & Vectors  2012;5:247.
Background
Aedes (Stegomyia) albopictus is currently one of the most notorious globally invasive mosquito species. Its medical importance is well documented, and its fast expansion throughout most continents is being monitored with concern. It is generally assumed that its expansion through the Western Pacific island countries has not progressed since its establishment in Fiji in 1989. However, the current status of Ae. albopictus in the Pacific region is largely unknown.
Findings
According to data from the literature and our own observations, Ae. albopictus is currently present in the following countries of the southern Pacific region: Papua New Guinea, Solomon Islands, Fiji, and the Kingdom of Tonga, where it was first detected in July 2011. It is absent from New Caledonia and French Polynesia where routine entomological surveillance is carried out, and was not detected during entomological work in 2007, either on the Cook Islands or on the Wallis and Futuna Islands. The species was not reported from American Samoa in 2004, but it is mentioned as probably present in Vanuatu. This is the first report of Ae. albopictus in Tonga.
Conclusions
The introduction and establishment of Ae. albopictus in Tonga was expected due to the geographical proximity of this country to Fiji where the species is strongly established. The pathway of introduction is unknown. The expansion of Ae. albopictus in the Pacific region poses an increasing threat to public health given the role this mosquito plays as primary vector of emerging infectious diseases such as Chikungunya fever.
doi:10.1186/1756-3305-5-247
PMCID: PMC3497854  PMID: 23130961
Aedes albopictus; Vector; Distribution; Pacific islands; Tonga; Introduction
13.  Prenatal Exposure to TCDD Triggers Significant Modulation of microRNA Expression Profile in the Thymus That Affects Consequent Gene Expression 
PLoS ONE  2012;7(9):e45054.
Background
MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand “the fetal basis of adult disease” hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.
Methodology/Principal Findings
miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3′-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.
Conclusions/Significance
These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development.
doi:10.1371/journal.pone.0045054
PMCID: PMC3443208  PMID: 23024791
14.  Resveratrol Prevents Endothelial Cells Injury in High-Dose Interleukin-2 Therapy against Melanoma 
PLoS ONE  2012;7(4):e35650.
Immunotherapy with high-dose interleukin-2 (HDIL-2) is an effective treatment for patients with metastatic melanoma and renal cell carcinoma. However, it is accompanied by severe toxicity involving endothelial cell injury and induction of vascular leak syndrome (VLS). In this study, we found that resveratrol, a plant polyphenol with anti-inflammatory and anti-cancer properties, was able to prevent the endothelial cell injury and inhibit the development of VLS while improving the efficacy of HDIL-2 therapy in the killing of metastasized melanoma. Specifically, C57BL/6 mice were injected with B16F10 cells followed by resveratrol by gavage the next day and continued treatment with resveratrol once a day. On day 9, mice received HDIL-2. On day 12, mice were evaluated for VLS and tumor metastasis. We found that resveratrol significantly inhibited the development of VLS in lung and liver by protecting endothelial cell integrity and preventing endothelial cells from undergoing apoptosis. The metastasis and growth of the tumor in lung were significantly inhibited by HDIL-2 and HDIL-2 + resveratrol treatment. Notably, HDIL-2 + resveratrol co-treatment was more effective in inhibiting tumor metastasis and growth than HDIL-2 treatment alone. We also analyzed the immune status of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSC) and FoxP3+CD4+ regulatory T cells (Treg). We found that resveratrol induced expansion and suppressive function of MDSC which inhibited the development of VLS after adoptive transfer. However, resveratrol suppressed the HDIL-2-induced expansion of Treg cells. We also found that resveratrol enhanced the susceptibility of melanoma to the cytotoxicity of IL-2-activated killer cells, and induced the expression of the tumor suppressor gene FoxO1. Our results suggested the potential use of resveratrol in HDIL-2 treatment against melanoma. We also demonstrated, for the first time, that MDSC is the dominant suppressor cell than regulatory T cell in the development of VLS.
doi:10.1371/journal.pone.0035650
PMCID: PMC3331985  PMID: 22532866
15.  Resveratrol (3,5,4'-trihydroxystilbene) protects pregnant mother and fetus from the immunotoxic effects of TCDD 
The “fetal basis of adult disease” hypothesis proposes that prenatal exposure to environmental stress can lead to increased susceptibility to clinical disorders later in life. Utero exposure of fetus to TCDD, leads to alterations in T cell differentiation in the thymus and increased susceptibility to autoimmune disease later in life. TCDD triggers a toxicity through activation of AhR and severely affects maternal immune system during pregnancy. In the current study, using a mouse model, we investigated if administration of resveratrol (RES) would inhibit immunotoxicity induced by TCDD during pregnancy in the mother and fetus. We observed that RES protected not only normal non-pregnant mice but also pregnant mothers and their fetuses from TCDD-induced thymic atrophy, apoptosis, and alterations in the expression of T cell receptor (TCR) and costimulatory molecules as well as T cell differentiation. Also, there was significantly reduced expression of CYP1A1 in thymi of both the mother and fetus when RES was used in vivo post-TCDD exposure. In conclusion, these studies demonstrate that consumption of RES, a natural plant product, during pregnancy, may afford protection to the mother and the fetus from the toxicity induced by environmental pollutants that mediate their effects through activation of AhR.
doi:10.1002/mnfr.201000206
PMCID: PMC3061307  PMID: 20715097
AhR; Fetus; Immunotoxicity; Resveratrol; TCDD
16.  Activation of Aryl Hydrocarbon Receptor (AhR) Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 Expression and Amelioration of Experimental Colitis 
PLoS ONE  2011;6(8):e23522.
Background
Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3+ Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis.
Methodology/Principal Findings
Dextran sodium sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3+ T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight) was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR+/+ but not AhR -/- mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment.
Conclusions/Significance
These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation.
doi:10.1371/journal.pone.0023522
PMCID: PMC3156147  PMID: 21858153
18.  Clinical evaluation of cissus quadrangularis and moringa oleifera and osteoseal as osteogenic agents in mandibular fracture 
Background:
Ayurveda the ancient science of medicine describes various herb preparations that achieve the hastening of bone healing. Harjor showed clinical efficacy in the treatment of fractures.
Objectives:
The comparative evaluation of herbal agents as osteogenic agents in mandibular fractures.
Study design:
The patients were divided into four groups. Group 1: Osteoseal; Group 3: Harjor (Cissus quadrangularis); Group 2: Moringa (Moringa Oleifera); Group 4: Placebo.
Result and Conclusion:
Pain, Swelling, Tenderness, Mobility reduction is maximum in Osteoseal group and minimum in Placebo. There was an increase in the serum calcium and phosphorus level at different follow-ups in each groups but there was a decrease in the placebo group. Ca, Ca+, Phosphrous increase was maximum in the group 1.
doi:10.4103/0975-5950.94466
PMCID: PMC3343389  PMID: 22639499
Osteogenic; prana; Asthisanghara
19.  American ginseng suppresses colitis through p53 mediated apoptosis of inflammatory cells 
Ulcerative colitis (UC) is a dynamic, chronic inflammatory condition associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism regulating UC. American ginseng (AG) is a putative anti-oxidant that can suppress hyperactive immune cells. We have recently shown that AG can prevent and treat mouse colitis. Because p53 levels are elevated in inflammatory cells in both mouse and human colitis, we tested the hypothesis that AG protects from colitis by driving inflammatory cell apoptosis through a p53 mechanism. We used isogenic p53+/+ and p53−/− inflammatory cell lines, as well as primary CD4+/CD25− effector T cells from p53+/+ and p53−/− mice to show that AG drives apoptosis in a p53-dependent manner. Moreover, we used a dextran sulfate sodium (DSS) model of colitis in C57BL/6 p53+/+ and p53−/− mice to test whether the protective effect of AG against colitis is p53-dependent. Data indicate AG induces apoptosis in p53+/+, but not in isogenic p53−/− cells in vitro. In vivo, C57BL/6 p53+/+ mice are responsive to the protective effects of AG against DSS-induced colitis, while AG fails to protect from colitis in p53−/− mice. Furthermore, TUNEL labeling of inflammatory cells within the colonic mesenteric lymph nodes is elevated in p53+/+ mice consuming DSS + AG, but not in p53−/− mice consuming DSS + AG. Results are consistent with our in vitro data, and with the hypothesis that AG drives inflammatory cell apoptosis in vivo, providing a mechanism by which AG protects from colitis in this DSS mouse model.
doi:10.1158/1940-6207.CAPR-09-0116
PMCID: PMC2833220  PMID: 20179294
p53; Inflammation; Ginseng; Colitis; Colon Cancer
20.  Epigenetic profile of the euchromatic region of human Y chromosome 
Nucleic Acids Research  2011;39(9):3594-3606.
The genome of a multi-cellular organism acquires various functional capabilities in different cell types by means of distinct chromatin modifications and packaging states. Acquired during early development, the cell type-specific epigenotype is maintained by cellular memory mechanisms that involve epigenetic modifications. Here we present the epigenetic status of the euchromatic region of the human Y chromosome that has mostly been ignored in earlier whole genome epigenetic mapping studies. Using ChIP-on-chip approach, we mapped H3K9ac, H3K9me3, H3K27me3 modifications and CTCF binding sites while DNA methylation analysis of selected CpG islands was done using bisulfite sequencing. The global pattern of histone modifications observed on the Y chromosome reflects the functional state and evolutionary history of the sequences that constitute it. The combination of histone and DNA modifications, along with CTCF association in some cases, reveals the transcriptional potential of all protein coding genes including the sex-determining gene SRY and the oncogene TSPY. We also observe preferential association of histone marks with different tandem repeats, suggesting their importance in genome organization and gene regulation. Our results present the first large scale epigenetic analysis of the human Y chromosome and link a number of cis-elements to epigenetic regulatory mechanisms, enabling an understanding of such mechanisms in Y chromosome linked disorders.
doi:10.1093/nar/gkq1342
PMCID: PMC3089472  PMID: 21252296
21.  Stem cells as potential therapeutic targets for inflammatory bowel disease 
The rates of incidence and prevalence of Crohn’s disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), are rising. Estimates indicate >1 million new cases of IBD in the United States annually. The conventional therapies available for IBD range from anti-inflammatory drugs to immunosuppressive agents, but these therapies generally fail to achieve satisfactory results due to their side effects. Interest in a new therapeutic option, that is, biological therapy, has gained much momentum recently due to its focus on different stages of the inflammatory process. Stem cell (SC) research has become a new direction for IBD therapy due to our recent understanding of cell populations involved in the pathogenic process. To this end, hematopoietic and mesenchymal stem cells are receiving more attention from IBD investigators. The intestinal environment, with its crypts and niches, supports incoming embryonic and hematopoietic stem cells and allows them to engraft and differentiate. The above findings suggest that, in the future, SC-based therapy will be a promising alternative to conventional therapy for IBD. In this review, we discuss SCs as potential therapeutic targets for future treatment of IBD.
PMCID: PMC2900153  PMID: 20515838
Inflammatory bowel disease; Crohn’s disease; Ulcerative Colitis; Stem cells; Review
22.  Taming the beast within: resveratrol suppresses colitis and prevents colon cancer 
Aging (Albany NY)  2010;2(4):183-184.
PMCID: PMC2881508  PMID: 20436227
Inflammation; complementary and alternative medicine; SIRT-1; NF-kappaB; inflammatory bowel disease
23.  Primary Peripheral T Cells Become Susceptible to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Mediated Apoptosis in Vitro upon Activation and in the Presence of Dendritic Cells 
Molecular pharmacology  2008;73(6):1722-1735.
Although the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cells in vivo have been well characterized, attempts to reproduce these findings in vitro have not been successful. In the current study, we examined whether activation or the presence of dendritic cells (DCs) would make primary naive T cells from C57BL/6 mice susceptible to TCDD-induced apoptosis in vitro. Although nonactivated primary T cells cultured with 10 to 1000 nM TCDD were relatively resistant to apoptosis, they became sensitive to apoptosis upon activation with concanavalin A (ConA). Moreover, ConA-activated T cells cultured in the presence of DCs showed highest levels of TCDD-induced apoptosis. Likewise, primary T cells from OT.II.2a mice cultured with specific ovalbumin peptide and syngeneic DCs showed higher levels of apoptosis compared with similar nonactivated T cells. T-cell activation led to up-regulation of aryl hydrocarbon receptor (AhR), Fas, and Fas-ligand (FasL) expression. In addition, DC maturation and culture with TCDD caused significant induction of FasL. TCDD-mediated apoptosis in activated peripheral T cells was AhR-dependent. Analysis of why nonactivated T cells are more resistant, whereas activated T cells are sensitive to TCDD-induced apoptosis revealed that TCDD treatment of activated but not nonactivated T cells led to down-regulation of cellular FLICE inhibitory protein (c-FLIP), an inhibitor of apoptosis. Moreover, down-regulation of c-FLIP using small interfering RNA in nonactivated T cells made them sensitive to TCDD-induced apoptosis. The current study demonstrates for the first time that TCDD can induce apoptosis in vitro in peripheral T cells upon activation and in the presence of DCs and that this may be mediated by down-regulation of c-FLIP.
doi:10.1124/mol.107.043406
PMCID: PMC2828294  PMID: 18334599
24.  Cloning and expression analysis of the Ccrboh gene encoding respiratory burst oxidase in Citrullus colocynthis and grafting onto Citrullus lanatus (watermelon) 
Journal of Experimental Botany  2010;61(6):1635-1642.
A full-length drought-responsive gene Ccrboh, encoding the respiratory burst oxidase homologue (rboh), was cloned in Citrullus colocynthis, a very drought-tolerant cucurbit species. The robh protein, also named NADPH oxidase, is conserved in plants and animals, and functions in the production of reactive oxygen species (ROS). The Ccrboh gene accumulated in a tissue-specific pattern when C. colocynthis was treated with PEG, abscisic acid (ABA), salicylic acid (SA), jasmonic acid (JA), or NaCl, while the homologous rboh gene did not show any change in C. lanatus var. lanatus, cultivated watermelon, during drought. Grafting experiments were conducted using C. colocynthis or C. lanatus as the rootstock or scion. Results showed that the rootstock significantly affects gene expression in the scion, and some signals might be transported from the root to the shoot. Ccrboh in C. colocynthis was found to function early during plant development, reaching high mRNA transcript levels 3 d after germination. The subcellular location of Ccrboh was investigated by transient expression of the 35S::Ccrboh::GFP fusion construct in protoplasts. The result confirmed that Ccrboh is a transmembrane protein. Our data suggest that Ccrboh might be functionally important during the acclimation of plants to stress and also in plant development. It holds great promise for improving drought tolerance of other cucurbit species.
doi:10.1093/jxb/erq031
PMCID: PMC2852657  PMID: 20181664
Citrullus colocynthis; C. lanatus; drought stress; grafting; NAPDH oxidase; RBOH; watermelon
25.  Natural dyes versus lysochrome dyes in cheiloscopy: A comparative evaluation 
Cheiloscopy is the study of lip prints. Lip prints are genotypically determined and are unique, and stable. At the site of crime, lip prints can be either visible or latent. To develop lip prints for study purpose various chemicals such as lysochrome dyes, fluorescent dyes, etc. are available which are very expensive. Vermilion (Sindoor used by married Indian women) and indigo dye (fabric whitener) are readily available, naturally derived, and cost-effective reagents available in India.
Objective:
To compare the efficacy of sudan black, vermilion, and indigo in developing visible and latent lip prints made on bone china cup, satin fabric, and cotton fabric.
Materials and Methods:
Out of 45 Volunteers 15 lip prints were made on bone China cup 15 lip prints on Satin fabric and 15 on Cotton fabric. Sudan black, vermilion and indigo were applied on visible and latent lip prints and graded as good (+,+), fair (+), and poor (-) and statistically evaluated.
Results:
The vermilion and indigo dye gives comparable results to that of sudan black for developing visible and latent lip prints.
doi:10.4103/0974-2948.71051
PMCID: PMC3009552  PMID: 21189984
Cheiloscopy; lip print; lipstick; sudan black; vermilion; indigo dye

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