Comparison of the efficacy of Icon resin infiltration and Clinpro XT varnish on remineralization of white spot lesions: An in-vitro study.

OBJECTIVE: To compare the efficacy of Icon resin infiltration and Clinpro XT varnish on remineralization of white spot lesions using a polarized light microscope (PLM). MATERIALS & METHODS: Artificial white spot lesions were created on a sample of 40 extracted human premolar teeth by immersing in a demineralizing solution. All samples were randomly allocated to two groups of 20 each; Group A: Icon resin infiltration and Group B: Clinpro XT varnish. Teeth were sectioned along the buccolingual plane using a diamond disc. Specimens were observed under the PLM (4× magnification) at three deepest measurements and their averages were calculated to obtain the mean penetration depth. The data obtained were analyzed using SPSS software (version 22.0). Independent samples t-test and group statistics were used to compare the two groups. In all statistical tests, the significance level was set at 5% (P < 0.05). RESULTS: Both Icon resin infiltration and Clinpro XT groups showed a statistically significant difference (P = 0.00) in the penetration depth. Icon resin infiltration group showed a significantly higher penetration depth (24.46 µm) compared to the Clinpro XT group (12.34 µm). Group A showed a greater mean penetration depth (17.07 ± 4.35 µm) when compared to group B (7.68 ± 1.81 µm). CONCLUSION: Icon resin infiltration showed a significantly higher penetration depth and is more effective on remineralization of white spot lesions when compared to Clinpro XT varnish.

Discovery of a potent cytotoxic agent that promotes G2/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line.

Squamous cell carcinoma is the major form of malignancy that arises in head and neck cancer. The modest improvement in the 5­year survival rate underpins its complex etiology and provides the impetus for the discovery of new therapeutics. The present study describes the discovery of an indole­based small molecule (24a) that was a potent cytotoxic agent with antiproliferative and pro­apoptotic properties against a pharyngeal carcinoma cell line, Detroit 562, effectively killing the cells at a half­maximal inhibitory concentration of 0.03 µM, as demonstrated using cell proliferation studies. The antiproliferative property of 24a was demonstrated by its ability to promote G2/M blockade, as assessed by cell cycle analysis using flow cytometry and the monitoring of real­time cell cycle progression by the fluorescence ubiquitination­based cell cycle indicator. This pro­apoptotic property is supported by the promotion of TUNEL­staining and increase in the activities of caspases­3/7 and ­6, in addition to the expression of death receptors and the cleavage of poly (ADP­ribose) polymerase 1 protein as demonstrated by western blotting. Given that Detroit 562 lacks functional p53, it is suggested that 24a acts independently of the tumor suppressor.

Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis.

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2'-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

TLR3-Dependent Activation of TLR2 Endogenous Ligands via the MyD88 Signaling Pathway Augments the Innate Immune Response.

The role of the adaptor molecule MyD88 is thought to be independent of Toll-like receptor 3 (TLR3) signaling. In this report, we demonstrate a previously unknown role of MyD88 in TLR3 signaling in inducing endogenous ligands of TLR2 to elicit innate immune responses. Of the various TLR ligands examined, the TLR3-specific ligand polyinosinic:polycytidylic acid (poly I:C), significantly induced TNF production and the upregulation of other TLR transcripts, in particular, TLR2. Accordingly, TLR3 stimulation also led to a significant upregulation of endogenous TLR2 ligands mainly, HMGB1 and Hsp60. By contrast, the silencing of TLR3 significantly downregulated MyD88 and TLR2 gene expression and pro-inflammatory IL1ß, TNF, and IL8 secretion. The silencing of MyD88 similarly led to the downregulation of TLR2, IL1ß, TNF and IL8, thus suggesting MyD88 to somehow act downstream of TLR3. Corroborating in vitro data, Myd88-/- knockout mice downregulated TNF, CXCL1; and phospho-p65 and phospho-IRF3 nuclear localization, upon poly I:C treatment in a mouse model of skin infection. Taken together, we identified a previously unknown role for MyD88 in the TLR3 signaling pathway, underlying the importance of TLRs and adapter protein interplay in modulating endogenous TLR ligands culminating in pro-inflammatory cytokine regulation.

Distinct Signaling Pathways Between Human Macrophages and Primary Gingival Epithelial Cells by Aggregatibacter actinomycetemcomitans.

In aggressive periodontitis, the dysbiotic microbial community in the subgingival crevice, which is abundant in Aggregatibacter actinomycetemcomitans, interacts with extra- and intracellular receptors of host cells, leading to exacerbated inflammation and subsequent tissue destruction. Our goal was to understand the innate immune interactions of A. actinomycetemcomitans with macrophages and human gingival epithelial cells (HGECs) on the signaling cascade involved in inflammasome and inflammatory responses. U937 macrophages and HGECs were co-cultured with A. actinomycetemcomitans strain Y4 and key signaling pathways were analyzed using real-time PCR, Western blotting and cytokine production by ELISA. A. actinomycetemcomitans infection upregulated the transcription of TLR2, TLR4, NOD2 and NLRP3 in U937 macrophages, but not in HGECs. Transcription of IL-1ß and IL-18 was upregulated in macrophages and HGECs after 1 h interaction with A. actinomycetemcomitans, but positive regulation persisted only in macrophages, resulting in the presence of IL-1ß in macrophage supernatant. Immunoblot data revealed that A. actinomycetemcomitans induced the phosphorylation of AKT and ERK1/2, possibly leading to activation of the NF-κB pathway in macrophages. On the other hand, HGEC signaling induced by A. actinomycetemcomitans was distinct, since AKT and 4EBP1 were phosphorylated after stimulation with A. actinomycetemcomitans, whereas ERK1/2 was not. Furthermore, A. actinomycetemcomitans was able to induce the cleavage of caspase-1 in U937 macrophages in an NRLP3-dependent pathway. Differences in host cell responses, such as those seen between HGECs and macrophages, suggested that survival of A. actinomycetemcomitans in periodontal tissues may be favored by its ability to differentially activate host cells.

In Vitro comparison of the microbial leakage of obturation systems: Epiphany with resilon, guttaflow, and ah plus with gutta percha.

AIM: To compare the microbial leakage of three root canal filling materials: AH Plus with Gutta-percha, Epiphany with Resilon, and Guttaflow using Enterococcus faecalis as the bacterial marker. MATERIALS AND METHODS: In total, 30 caries free, human maxillary incisors with straight roots were used. The teeth were de-coronated with a diamond disc and the length was standardized for all specimens. Access opening was done through the coronal portion and the working length was determined. All the teeth were prepared to a standardized size apically and coronally. The teeth were then randomly divided into three experimental groups each. After obturation of the root canals, the outer surfaces of the teeth were coated with two layers of nail enamel except the apical 2 mm. The teeth were then subjected for bacterial leakage test using E. faecalis as a bacterial marker in dual chamber bacterial leakage model for a period of 30 days. STATISTICAL ANALYSIS USED: Chi-square test. RESULTS: Results showed that Resilon/Epiphany (Group-2) demonstrated less leakage and Gutta-percha/AH Plus (Group-1) showed maximum leakage with the statistically significant difference between the two (P < 0.05). Guttaflow (Group-3) also showed less leakage than Gutta-percha/AH Plus (Group-1) with the statistically significant difference between the two (P < 0.05). There was no statistically significant difference between Resilon/Epiphany (Group-2) and Guttaflow (Group-3). CONCLUSION: Resilon/Epiphany and Guttaflow groups demonstrated less microbial leakage than Gutta-percha/AH Plus group.

IFN-ß secretion is through TLR3 but not TLR4 in human gingival epithelial cells.

The oral cavity is home for a plethora of bacteria and viruses. Epithelial barriers encounter these micro-organisms and recognize them via pathogen recognition receptors (PRRs) that instigate antibacterial and antiviral responses. We and others have shown that human gingival epithelial cells (HGECs) express PRRs to defend invading pathogens. Among these PRRs, TLR2, TLR3 and TLR4 are highly expressed in HGECs and appear to be important based on our previous findings. IFN-ß is one of the major type 1 interferons induced to defend viral attack. In this report, we sought to dissect TLR3 and TLR4 mediated secretion of IFN-ß in HGECs. We stimulated HGECs with ultrapure LPS (TLR4 ligand) and Poly I:C (TLR3 ligand) for 24 h and supernatant was used to determine IFN-ß secretion. We show that cells treated with Poly I:C induced IFN-ß secretion but not cells treated with LPS. In addition, silencing of TLR3 prior to Poly I:C stimulation significantly downregulated IFN-ß secretion. On the contrary, overexpression of MD2 and TLR4 in HGECs restored IFN-ß secretion. Upon further evaluation, we found that TLR3 stimulation but not TLR4 induced the phosphorylation of interferon regulatory factor 3 (IRF3), which is critical for IFN-ß secretion. We conclude that IFN-ß secretion is through TLR3 and not via TLR4 in HGECs.

Role of NOD1/NOD2 receptors in Fusobacterium nucleatum mediated NETosis.

Polymorphonuclear neutrophils (PMNs) are indispensable in fighting infectious microbes by adopting various antimicrobial strategies including phagocytosis and neutrophil extracellular traps (NETs). Although the role and importance of PMNs in periodontal disease are well established, the specific molecular mechanisms involved in NET formation are yet to be characterized. In the present study, we sought to determine the role of periodontal pathogen on NET formation by utilizing Fusobacterium nucleatum. Our data demonstrates that F. nucleatum activates neutrophils and induces robust NETosis in a time-dependent manner via the upregulation of the Nucleotide oligomerization domain 1 (NOD1) and NOD2 receptors. Furthermore, CRISPR/Cas9 knockout of HL-60 cells and the use of ligands/inhibitors confirmed the involvement of NOD1 and NOD2 receptors in F. nucleatum-mediated NET formation. When treated with NOD1 and NOD2 inhibitors, we observed a significant downregulation of peptidylarginine deiminase 4 (PAD4) activity. In addition, neutrophils showed a significant increase and decrease of myeloperoxidase (MPO) and neutrophil elastase (NE) when treated with NOD1/NOD2 ligands and inhibitors, respectively. Taken together, CRISPR/Cas9 knockout of NOD1/NOD2 HL-60 cells and inhibitors of NOD signaling confirmed the role of NLRs in F. nucleatum-mediated NETosis. Our data demonstrates an important pathway linking NOD1 and NOD2 to NETosis by F. nucleatum, a prominent microbe in periodontal biofilms. This is the first study to elucidate the role of NOD-like receptors in NETosis and their downstream signaling network.

Effect of yoga on cardiac autonomic dysfunction and insulin resistance in non-diabetic offspring of type-2-diabetes parents: A randomized controlled study.

OBJECTIVE: The present study was aimed to determine the effect of yoga program on cardiac autonomic dysfunction and insulin resistance in non-diabetic offspring of diabetes parents. METHODS: A randomized passive-controlled study was conducted on 64 non-diabetic offspring of type-2-diabetes parents (mean-age:25.17years). Yoga group participants received yoga training for 8 weeks. Heart-rate variability (HRV) indices: low frequency (LF), high frequency (HF) and LF/HF ratio; fasting blood glucose (FBG), oral glucose tolerance test (OGTT) and insulin resistance (IR) were estimated at baseline and after 8-weeks of intervention. RESULTS: We found a significant decrease in LF (p = 0.005), LF/HF ratio (p = 0.004), IR (p < 0.001), OGTT (p = 0.003) and increase in HF (p = 0.022) in yoga group participants. Control group participants did not show any significant change in any variables. CONCLUSIONS: Improvement in cardiac autonomic function and insulin resistance by yoga training implies that yoga can reduce the risk of development of diabetes in offspring of diabetes parents.

Protective effects of Ethanolic Extract of Emblica officinalis (amla) on Cardiovascular Pathophysiology of Rats, Fed with High Fat Diet.

INTRODUCTION: Dietary high fat alters lipid profile and possibly induce sympatho-vagal imbalance. Emblica officinalis is found to be potential antioxidant and possibly counteract hyperlipidemia induced lipid peroxidation. AIM: To assess Ethanolic extract of Emblica Officinalis (EEO) as lipid lowering and cardiovascular protective agent against high dietary fat supplemented to experimental rats. Further to study a comparative analysis between EEO and atorvastatin on hyperlipidemia and cardiovascular integrity. MATERIALS AND METHODS: EEO was prepared and phytochemical analysis was done. Rats were divided into five groups, having six rats in each group as following; Group I-control (20% fat); Group II (+ EEO 100 mg/kg body wt); Group III (fed with high fat diet; 30% fat); Group IV (fed with high fat diet; 30% fat + EEO 100 mg/kg body wt) and Group V (fed with high fat diet; 30% fat + atorvastatin 4 mg/kg body wt). The treatments were continued for 21 days. Gravimetric parameters and electrophysiological parameters {Heart Rate (HR), sympatho-vagal balance} were recorded and lipid profiles of all the groups were measured. ANOVA, correlation and multiple regressions were done for analysis of data. RESULTS: Significant alteration in serum lipid profile was observed in rats fed with high dietary fat but supplementation of EEO was found to be reversible. Electrophysiological evaluation revealed altered HR and sympatho-vagal balance in high dietary fat fed rats (Group III) which indicate cardiac autonomic malfunctions which were found to be improved in Emblica officinalis supplemented group of rats (Group IV). Further, analysis has shown significant negative correlation between HDL/LDL and sympatho-vagal balance in all groups of rats which clearly indicate a role of dietary fat on sympatho-vagal balance. These results further corroborated with findings of histopathological study on myocardium and elastic artery. CONCLUSION: Observations from the study indicate a beneficial role of ethanolic extract of Emblica officinalis (amla) on dyslipidemia and cardiac autonomic functions in rats treated with high fat diet.

Comparison of yoga and walking-exercise on cardiac time intervals as a measure of cardiac function in elderly with increased pulse pressure.

OBJECTIVE: Arterial aging along with increased blood pressure(BP) has become the major cardiovascular(CV) risk in elderly. The aim of the study was to compare the effects of yoga program and walking-exercise on cardiac function in elderly with increased pulse pressure (PP). METHODS: An open label, parallel-group randomized controlled study design was adopted. Elderly individuals aged ≥60 years with PP≥60mmHg were recruited for the study. Yoga (study) group (n=30) was assigned for yoga training and walking (exercise) group (n=30) for walking with loosening practices for one hour in the morning for 6days in a week for 3 months. The outcome measures were cardiac time intervals derived from pulse wave analysis and ECG: resting heart rate (RHR), diastolic time(DT), ventricular ejection time(LVET), upstroke time(UT), ejection duration index (ED%), pre-ejection period (PEP), rate pressure product (RPP) and percentage of mean arterial pressure (%MAP). RESULTS: The mean within-yoga group change in RHR(bpm) was 4.41 (p=0.031), PD(ms): -50.29 (p=0.042), DT(ms): -49.04 (p=0.017), ED%: 2.107 (p=0.001), ES(mmHg/ms): 14.62 (p=0.118), ET(ms): -0.66 (p=0.903), UT(ms): -2.54 (p=0.676), PEP(ms): -1.25 (p=0.11) and %MAP: 2.08 (p=0.04). The mean within-control group change in HR (bpm) was 0.35 (p=0.887), PD (ms): 11.15(p=0.717), DT (ms): 11.3 (p=0.706), ED%: -0.101 (p=0.936), ES (mmHg/ms): 0.75 (p=0.926), ET(ms): 2.2 (p=0.721), UT(ms):4.7(p=455), PEP (ms): 2.1(p=0.11), %MAP: 0.65 (p=0.451). A significant difference between-group was found in RHR (p=0.036), PD (p=0.02), ED% (p=0.049), LVET (p=0.048), DT (p=0.02) and RPP (p=0.001). CONCLUSIONS: Yoga practice for 3 months showed a significant improvement in diastolic function with a minimal change in systolic function. Yoga is more effective than walking in improving cardiac function in elderly with high PP.

Investigation of the functional role of human Interleukin-8 gene haplotypes by CRISPR/Cas9 mediated genome editing.

Interleukin-8 (IL-8) gene polymorphisms have been considered as susceptibility factors in periodontal disease. However, the functional roles of IL-8 gene haplotypes have not been investigated. Here, we demonstrate for the first time the use of the CRISPR/Cas9 system to engineer the IL-8 gene, and tested the functionality of different haplotypes. Two sgRNAs vectors targeting the IL-8 gene and the naked homologous repair DNA carrying different haplotypes were used to successfully generate HEK293T cells carrying the AT genotype at the first SNP - rs4073 (alias -251), TT genotype at the second SNP - rs2227307 (alias +396), TC or CC genotypes at the third SNP - rs2227306 (alias +781) at the IL-8 locus. When stimulated with Poly I:C, ATC/TTC haplotype, cells significantly up-regulated the IL-8 at both transcriptional and translational levels. To test whether ATC/TTC haplotype is functional, we used a trans-well assay to measure the transmigration of primary neutrophils incubated with supernatants from the Poly I:C stimulation experiment. ATC/TTC haplotype cells significantly increased transmigration of neutrophils confirming the functional role for this IL-8 haplotype. Taken together, our data provides evidence that carriage of the ATC/TTC haplotype in itself may increase the influx of neutrophils in inflammatory lesions and influence disease susceptibility.

A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. METHODS: Sixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. RESULTS: Both baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. CONCLUSION: The present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative.

A randomized, comparative, open-label study of efficacy and tolerability of alfuzosin, tamsulosin and silodosin in benign prostatic hyperplasia.

OBJECTIVES: Benign prostatic hyperplasia (BPH) is a common and progressive disease affecting elderly males, often associated with lower urinary tract symptoms (LUTS). α1-blockers are the mainstay in symptomatic therapy of BPH. Because of their greater uroselectivity and minimal hemodynamic effects, alfuzosin, tamsulosin, and silodosin are generally preferred. The aim of this study was to compare the efficacy and tolerability of alfuzosin, tamsulosin, and silodosin in patients with BPH and LUTS. METHODS: Ninety subjects with BPH and LUTS were randomized into three groups of thirty in each, to receive alfuzosin sustained release (SR) 10 mg, tamsulosin 0.4 mg, or silodosin 8 mg for 12 weeks. The primary outcome measure was a change in the International Prostate Symptom Score (IPSS), and the secondary outcome measures were changes in individual subjective symptom scores, quality of life score (QLS), and peak flow rate (Qmax) from baseline. The treatment response was monitored at 2, 4, 8, and 12 weeks. RESULTS: IPSS improved by 88.18%, 72.12%, and 82.23% in alfuzosin SR, tamsulosin and silodosin groups (P < 0.001) at 12 weeks. Improvement in QLS was >75% in all the three groups (P < 0.001). A significant improvement in Qmax was seen with alfuzosin and tamsulosin (P = 0.025 and P < 0.001) but not with silodosin (P = 0.153). However, the intergroup differences in IPSS, QLS, and Qmax were not significant. Ejaculatory dysfunction was more common with silodosin and corrected QT (QTc) prolongation occurred only with alfuzosin (two subjects) and tamsulosin (three subjects). CONCLUSION: Alfuzosin, tamsulosin, and silodosin showed similar efficacy in improvement of LUTS secondary to BPH, with good tolerability, acceptability, and minimum hemodynamic adverse effects. Alfuzosin, tamsulosin, and silodosin are comparable in efficacy in symptomatic management of BPH. The occurrence of QTc prolongation in three subjects with tamsulosin in the present study is an unexpected adverse event as there are no reports of QTc prolongation with tamsulosin in any of the previous studies.

Different anthropometric adiposity measures and their association with cardiovascular disease risk factors in middle aged women.

A cross sectional study of 136 women age group40-55 years was conducted to study which anthropometric measure had the strongest association with cardiovascular disease risk factors in middle aged women. In accordance with their BMI measurement subjects were divided into three groups namely: Normal weight (Group1) BMI 18.5-24.9 kg/m2, Overweight (Group2) - 25 kg/m2 - 29.9 kg/m2, Obese (Group3) - BMI > 30 kg/m2. Each group was further divided into premenopausal and postmenopausal women BMI, WHR, WHtR, SBP, DBP were recorded. TG, TC, HDL and FBS values were estimated. Results showed that both pre and post menopausal middle aged obese women with higher BMI, WHR and WHtR have more chances of having cardiovascular diseases. BMI, WHR and WHtR are theeasy and practical methods to diagnose obesity and together can be used as simple measures to predict cardiovascular risk factors in middle aged women.

Effect of yoga on arterial stiffness in elderly subjects with increased pulse pressure: A randomized controlled study.

OBJECTIVE: We aimed to determine the effect of yoga on arterial function in elderly with increased pulse pressure (PP). DESIGN: Randomized controlled study with two parallel groups. PARTICIPANTS: Elderly subjects with PP≥60 mmHg (n=60). INTERVENTIONS: Yoga group (n=30) was assigned for yoga training and brisk-walking (BW) group (n=30) for brisk-walk with stretching exercise for 1h in the morning for 6 days in a week for 12 weeks. MAIN OUTCOME MEASURES: Arterial stiffness measures: Brachial-ankle pulse wave velocity (baPWV), Carotid-femoral pulse wave velocity (c-f PWV), aortic augmentation index (AIx@75), arterial stiffness index at brachial (bASI) and tibial arteries (aASI). Total serum nitric oxide concentration (NOx) as an index of endothelial function. Heart rate variability (HRV) measures: Low frequency and high frequency in normalized units (LFnu, HFnu) and LF/HF ratio. RESULTS: The mean between-group change (with 95% CI) in arterial stiffness: c-f PWV(m/s) [1.25(0.59-1.89); p<0.001], baPWV(m/s) [1.96(0.76-3.16), p<0.01], AIx@75 [3.07(0.24-5.89), p=0.066], aASI [8.3(4.06-12.53), p<0.001]; endothelial function index: NO(µmol/L) [-9.03(-14.57 to -3.47), p<0.001]; SBP(mmHg) [14.23(12.03-16.44), p<0.001], DBP(mmHg) [0.1(-1.95-2.15), p=0.38], PP(mmHg) [14.07(11.2-16.92), p<0.001], MAP(mmHg) [4.7(3.08-6.32), p<0.001]; and cardiac autonomic function: LF(nu) [4.81(1.54-8.08), p<0.01], HF(nu) [-4.13(-7.57 to -0.69), p<0.01], LF/HF ratio [0.84(0.3-1.37), p<0.001], indicate significant difference in effects of two intervention on arterial stiffness, endothelial function, BP and cardiac autonomic activity. There was significant change within-yoga group in vascular function, BP and autonomic function, while no significant change within-BW group was observed. CONCLUSION: Our findings suggest that yoga program offered was more effective than brisk-walk in reducing arterial stiffness along with BP in elderly individuals with increased PP. Yoga can also significantly reduce sympathetic activity and improve endothelial function with enhancement in bioavailability of NO.

The B Cell-Stimulatory Cytokines BLyS and APRIL Are Elevated in Human Periodontitis and Are Required for B Cell-Dependent Bone Loss in Experimental Murine Periodontitis.

B-lineage cells (B lymphocytes and plasma cells) predominate in the inflammatory infiltrate of human chronic periodontitis. However, their role in disease pathogenesis and the factors responsible for their persistence in chronic lesions are poorly understood. In this regard, two cytokines of the TNF ligand superfamily, a proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), are important for the survival, proliferation, and maturation of B cells. Thus, we hypothesized that APRIL and/or BLyS are upregulated in periodontitis and contribute to induction of periodontal bone loss. This hypothesis was addressed in both human and mouse experimental systems. We show that, relative to healthy controls, the expression of APRIL and BLyS mRNA and protein was upregulated in natural and experimental periodontitis in humans and mice, respectively. The elevated expression of these cytokines correlated with increased numbers of B cells/plasma cells in both species. Moreover, APRIL and BLyS partially colocalized with κ L chain-expressing B-lineage cells at the epithelial-connective tissue interface. Ligature-induced periodontitis resulted in significantly less bone loss in B cell-deficient mice compared with wild-type controls. Ab-mediated neutralization of APRIL or BLyS diminished the number of B cells in the gingival tissue and inhibited bone loss in wild-type, but not in B cell-deficient, mice. In conclusion, B cells and specific cytokines involved in their growth and differentiation contribute to periodontal bone loss. Moreover, APRIL and BLyS have been identified as potential therapeutic targets in periodontitis.

Effect of yoga on oxidative stress in elderly with grade-I hypertension: a randomized controlled study.

BACKGROUND AND OBJECTIVES: Hypertension, especially in elderly is a strong risk factor for cardiovascular mortality and morbidity. Oxidative stress has been implicated as one of the underlying cause of hypertension. Yoga has been found to control hypertension in the elderly, but the underlying benefits of mechanism in relation to oxidative stress regulation remains unclear. The purpose of the study was to investigate the effect of yoga on oxidative stress in elderly with Grade-I hypertension. METHODS: An open parallel-arm randomised controlled study was conducted at BLDE University's Shri B.M.Patil Medical College, Hospital and Research Centre, India on elderly male individuals with Grade-I hypertension (n=57, age 60-80 years). Study (Yoga) group was assigned for yoga intervention and control group for walking for one hour in the morning for six days in a week for three months under the supervision of yoga instructor and physical training instructor respectively. Serum malondialdehyde (MDA) as an indicator of oxidative stress and antioxidants such as serum superoxide dismutase (SOD), reduced glutathione (GSH) and vitamin C levels were estimated. RESULTS: Yoga practice for three months has significantly reduced serum MDA level (p<0.001), and enhanced antioxidants level such as SOD activity (p=0.007), serum GSH (p=0.002) and vitamin C (p=0.002). In the control group, we observed a significant increase in serum MDA level (p=0.04) and reduction in serum vitamin C level (p=0.015) with no significant difference in the SOD activity and GSH level. CONCLUSION: These findings suggest that yoga is an effective means to reduce oxidative stress and to improve antioxidant defense in elderly hypertensive individuals.

P. gingivalis modulates keratinocytes through FOXO transcription factors.

P. gingivalis is a prominent periodontal pathogen that has potent effects on host cells. In this study we challenged gingival epithelial cells with P. gingivalis with the aim of assessing how mRNA levels of key target genes were modulated by P. gingivalis via the transcription factors FOXO1 and FOXO3. Primary mono- and multi-layer cultures of gingival epithelial cells were challenged and barrier function was examined by fluorescent dextran and apoptosis was measured by cytoplasmic histone associated DNA. Gene expression levels were measured by real-time PCR with and without FOXO1 and FOXO3 siRNA compared to scrambled siRNA. P. gingivalis induced a loss of barrier function and stimulated gingival epithelial cell apoptosis in multilayer cultures that was in part gingipain dependent. P. gingivalis stimulated an increase in FOXO1 and FOXO3 mRNA, enhanced mRNA levels of genes associated with differentiated keratinocyte function (keratin-1, -10, -14, and involucrin), increased mRNA levels of apoptotic genes (BID and TRADD), reduced mRNA levels of genes that regulate inflammation (TLR-2 and -4) and reduced those associated with barrier function (integrin beta-1, -3 and -6). The ability of P. gingivalis to modulate these genes was predominantly FOXO1 and FOXO3 dependent. The results indicate that P. gingivalis has pronounced effects on gingival keratinocytes and modulates mRNA levels of genes that affect host response, differentiation, apoptosis and barrier function. Moreover, this modulation is dependent upon the transcription factors FOXO1 or FOXO3. In addition, a new function for FOXO1 was identified, that of suppressing TLR-2 and TLR-4 and maintaining integrin beta -1, beta -3 and beta -6 basal mRNA levels in keratinocytes.

Effect of yoga on short-term heart rate variability measure as a stress index in subjunior cyclists: a pilot study.

Subjunior athletes experience mental stress due to pressure from the coach, teachers and parents for better performance. Stress, if remains for longer period and not managed appropriately can leads to negative physical, mental and cognitive impact on children. The present study was aimed to evaluate the effect of integrated yoga module on heart rate variability (HRV) measure as a stress index in subjunior cyclists. Fast furrier transform technique of frequency domain method was used for the analysis of HRV. We have found a significant increase in high frequency (HF) component by 14.64% (P < 0.05) and decrease in the low frequency component (LF) of HRV spectrum by 5.52% (P < 0.05) and a decrease in LF/HF ratio by 19.63% (P < 0.01) in yoga group. In the control group, there was decrease in the HF component and, no significant difference in the LF component of HRV spectrum and LF/HF ratio. The results show that yoga practice decreases sympathetic activity and causes a shift in the autonomic balance towards parasympathetic dominance indicating a reduction in stress. In conclusion, yoga practice helps to reduce stress by optimizing the autonomic functions. So, it is suggested to incorporate yoga module as a regular feature to keep subjunior athletes both mentally and physically fit.