BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic, premalignant condition of the oral mucosa and one of the commonest potentially malignant disorders amongst the Asian population. The objective of this study was to investigate the association of etiologic factors with: age, frequency, duration of consumption of areca nut and its derivatives, and the severity of clinical manifestations. METHODS: A cross-sectional, multi centric study was conducted over 8 years on clinically diagnosed OSMF cases (n = 765) from both public and private tertiary care centers. Sample size was determined by World Health Organization sample size calculator. Consumption of areca nut in different forms, frequency of daily usage, years of chewing, degree of mouth opening and duration of the condition were recorded. Level of significance was kept at P < or = 0.05. RESULTS: A total of 765 patients of OSMF were examined, of whom 396 (51.8%) were male and 369 (48.2%) female with a mean age of 29.17 years. Mild OSMF was seen in 61 cases (8.0%), moderate OSMF in 353 (46.1%) and severe OSMF in 417 (54.5%) subjects. Areca nut and other derivatives were most frequently consumed and showed significant risk in the severity of OSMF (P < or = 0.0001). Age of the sample and duration of chewing years were also significant (P = 0.012). CONCLUSIONS: The relative risk of OSMF increased with duration and frequency of areca nut consumption especially from an early age of onset.
Age of Onset ; Areca* ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Mastication ; Mouth ; Mouth Mucosa ; Nuts* ; Oral Submucous Fibrosis* ; Pakistan* ; Sample Size ; Tertiary Care Centers ; World Health Organization

BACKGROUND: To assess and compare the salivary flow rate (SFR) and salivary pH among areca nut chewers, oral submucous fibrosis (OSMF) patients and apparently healthy individuals. METHODS: A comparative study was conducted to assess and compare the SFR and pH among 135 outpatients (45 areca nut chewers + 45 OSMF + 45 control) at The Oxford Dental College and Research Hospital, Bangalore, India. Subjects were interviewed using structural proforma and Modified Schirmer strips and pH paper were implemented for assessing SFR and pH respectively. Statistical analysis was done using IBM SPSS ver. 21.0 software. RESULTS: A statistically significant increase in SFR (35.7 mm at 3rd minutes) among areca nut group and a decrease in SFR among OSMF group (23.4 mm at 3rd minutes) when compared to apparently healthy subjects (30.7 mm at 3rd minutes). The mean pH among areca nut, OSMF and control groups was 6.76, 6.82, and 6.74 respectively with no statistical significance. CONCLUSIONS: The observation and findings of the study clearly showed hypersalivation among areca nut group and hyposalivation among OSMF group, with no significant change in salivary pH when compared to healthy subjects.
Areca* ; Humans ; Hydrogen-Ion Concentration* ; India ; Nuts* ; Oral Submucous Fibrosis* ; Outpatients ; Saliva ; Sialorrhea ; Xerostomia

BACKGROUND: Quercetin, found abundantly in onion peel, has been known to have anticholesterol, antithrombotic and insulin-sensitizing properties. Here, we investigated the effect of quercetin-rich onion peel extract (OPE) on reactive oxygen species (ROS) production and antioxidative defense in obese woman. METHODS: This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were randomly assigned that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. ROS production and superoxide dismutase (SOD) activity in plasma were determined by using ROS and SOD assay kits, respectively. RESULTS: Baseline characteristics of anthropometric indicators and blood metabolic profiles were not significantly different between the two groups. Compared with baseline values, OPE consumption significantly reduced waist and hip circumference. Plasma ROS level and SOD activity were decreased in both placebo and OPE groups compared with baseline values. However, plasma ROS level in OPE group was significantly lower than in placebo group while plasma SOD activity in OPE group was significantly higher than in placebo group after 12 weeks of consumption. CONCLUSIONS: These findings indicate that OPE consumption may exert antioxidative effect by preventing the decrease of SOD activity as well as the production of ROS in obese women.
Female ; Hip ; Humans ; Metabolome ; Onions* ; Plasma ; Quercetin ; Reactive Oxygen Species ; Superoxide Dismutase

BACKGROUND: Anthocyanins have been shown to inhibit cancer cell growth by suppressing oxidative stress and inflammatory responses. The purpose of this study was to investigate the effects of an anthocyanin-rich extract (AE) from black soybean coat on intestinal carcinogenesis. METHODS: APC(Min/+) mice were fed a diet of 0.2% or 0.5% AE for 7 weeks. We analyzed the number of intestinal tumors, oxidative stress and inflammatory markers associated with beta-catenin and cytosolic phospholipase A2 (cPLA2) signals. The number of intestinal tumors, and cellular expression of beta-catenin were determined. RESULTS: The number of intestinal tumors was significantly lower in mice fed a 0.5% AE diet compared to those of the other groups. Cytosolic beta-catenin expression was significantly decreased in the AE supplemented groups compared to that of the control animals. In addition, mucosa expression of cyclooxygenase-2 and cPLA2 were also significantly decreased in the 0.5% AE group, by 32% and 62%, respectively, compared to the control group. CONCLUSIONS: These results suggest that dietary AE reduced the development of intestinal tumors, possibly through the ability to suppress oxidative stresses, decreasing inflammatory responses mediated by beta-catenin associated signals.
Animals ; Anthocyanins ; beta Catenin ; Carcinogenesis ; Cyclooxygenase 2 ; Cytosol ; Diet ; Inflammation ; Intestinal Polyposis* ; Mice ; Mucous Membrane ; Oxidative Stress ; Phospholipases A2 ; Soybeans*

BACKGROUND: Withania somnifera (known as Ashwagandha) is a medicinal plant used in the ayurvedic medicines in India. Withaferin-A, a withanolide derived from the leaf extract of W. somnifera, has been reported to exhibit anti-tumor activity against various cancer cells, such as leukemia, breast cancer and colon cancer cells. METHODS: We investigated the anti-cancer effects of withaferin-A on the proliferation and migration of human colorectal cancer (HCT116) cells. And we evaluated the effects of withaferin-A on the transcriptional activity of STAT3 and the growth of HCT116 cells in xenograft mouse tumor model. RESULTS: In the present study, we found that withaferin-A inhibited the proliferation and migration of HCT116 cells in a concentration-dependent manner. Treatment of HCT116 cells with withaferin-A attenuated interleukin-6-induced activation of STAT3, which has been implicated in the development and progression of colon cancer. To examine the effect of withaferin-A on HCT116 cells proliferation in vivo, we generated HCT116 cells xenograft tumors in Balb/c nude mice and treated the tumor bearing mice with or without withaferin-A intraperitoneally. Treatment with withaferin-A exhibited significant decrease in the volume and weight of tumors as compared to untreated controls. CONCLUSIONS: The present study suggests that withaferin-A holds the potential to be developed as a small molecule inhibitor of STAT3 for the treatment of HCT116.
Animals ; Breast Neoplasms ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; HCT116 Cells ; Heterografts ; Humans ; India ; Leukemia ; Mice ; Mice, Nude ; Plants, Medicinal ; STAT3 Transcription Factor ; Withania

BACKGROUND: The Janus kinase (Jak)/Signal transducers of activated transcription (Stat) pathway is an upstream signaling pathway for NF-kappaB activation in Helicobacter pylori-induced interleukin (IL)-8 production in gastric epithelial AGS cells. H. pylori activates NADPH oxidase and produces hydrogen peroxide, which activates Jak1/Stat3 in AGS cells. Therefore, hydrogen peroxide may be critical for IL-8 production via Jak/Stat activation in gastric epithelial cells. Glutamine is depleted during severe injury and stress and contributes to the formation of glutathione (GSH), which is involved in conversion of hydrogen peroxide into water as a cofactor for GSH peroxidase. METHODS: We investigated whether glutamine deprivation induces hydrogen peroxide-mediated IL-8 production and whether hydrogen peroxide activates Jak1/Stat3 to induce IL-8 in AGS cells. Cells were cultured in the presence or absence of glutamine or hydrogen peroxide, with or without GSH or a the Jak/Stat specific inhibitor AG490. RESULTS: Glutamine deprivation decreased GSH levels, but increased levels of hydrogen peroxide and IL-8, an effect that was inhibited by treatment with GSH. Hydrogen peroxide induced the activation of Jak1/Stat3 time-dependently. AG490 suppressed hydrogen peroxideinduced activation of Jak1/Stat3 and IL-8 expression in AGS cells, but did not affect levels of reactive oxygen species in AGS cells. CONCLUSIONS: In gastric epithelial AGS cells, glutamine deprivation increases hydrogen peroxide levels and IL-8 expression, which may be mediated by Jak1/Stat3 activation. Glutamine supplementation may be beneficial for preventing gastric inflammation by suppressing hydrogen peroxide-mediated Jak1/Stat3 activation and therefore, reducing IL-8 production. Scavenging hydrogen peroxide or targeting Jak1/Stat3 may also prevent oxidant-mediated gastric inflammation.
Epithelial Cells ; Glutamine* ; Glutathione ; Helicobacter ; Hydrogen Peroxide ; Hydrogen* ; Inflammation ; Interleukin-8* ; Interleukins ; NADPH Oxidase ; NF-kappa B ; Peroxidase ; Phosphotransferases ; Reactive Oxygen Species ; Transducers ; Water

Stomach cancer remains, stubbornly, highly prevalent in East Asia. Still, stomach cancer has few biomarkers by which it can be predicted. Helicobacter pylori infection, a known carcinogen of stomach cancer, usually goes undetected prior to cancer diagnosis, due to the poor mucosal environments that its related gastric atrophy causes. We propose, herein, an endoscopic-biopsy-based cancer-predicting DNA methylation marker. We semi-quantitatively examined the methylation-variable sites near the CpG-island margins by radioisotope-labeling methylation-specific polymerase chain reaction in association with H. pylori, which increases age-related over-methylation in CpG islands of gastric mucosa. These age-related methylation patterns of the transitional-CpG sites are proposed as useful surrogate markers for stomach cancer. It would be helpful for setting the optimal screening interval for high-risk subjects as well as for estimating the prognosis and the predictability for recurrence of early gastric cancer in patients having undergone endoscopic submucosal dissection. New screening-interval guidelines for gastric cancer should be suggested considering individual risk based on age, severity of atrophy, H. pylori status, and DNA methylation pattern.
Atrophy ; Biomarkers* ; CpG Islands ; Diagnosis ; DNA Methylation* ; DNA* ; Far East ; Gastric Mucosa ; Helicobacter pylori ; Humans ; Mass Screening ; Methylation ; Polymerase Chain Reaction ; Prognosis ; Recurrence ; Stomach Neoplasms*

RSK2 is a downstream signaling protein of ERK1 and ERK2 and plays a key role in physiological homeostasis. For this reason, RSK2 is a highly conserved protein among the p90RSK family members. In its location in the signaling pathway, RSK2 is a kinase just upstream of transcription and epigenetic factors, and a few kinases involved in cell cycle regulation and protein synthesis. Moreover, activation of RSK2 by growth factors is directly involved in cell proliferation, anchorage-independent cell transformation and cancer development. Direct evidences regarding the etiological roles of RSK2 in cancer development in humans have been published by our research group illustrating that elevated total- and phospho-RSK2 protein levels mediated by ERK1 and ERK2 are higher in skin cancer tissues compared to normal skin tissues. Notably, it has been shown that RSK2 ectopic expression in JB6 Cl41 cells induces cell proliferation and anchorage-independent cell transformation. Importantly, knockdown of RSK2 suppresses Ras-mediated foci formation and anchorage-independent colony growth of cancer cells. Kaempferol is a one of the natural compounds showing selectivity in inhibiting RSK2 activity in epidermal growth factor-induced G1/S cell cycle transition and cell transformation. Thus, ERKs/RSK2 signaling axis is an important target signaling molecule in chemoprevention.
Axis, Cervical Vertebra* ; Carcinogenesis ; Cell Cycle ; Cell Proliferation ; Cell Transformation, Neoplastic ; Chemoprevention ; Epigenomics ; Homeostasis ; Humans ; Intercellular Signaling Peptides and Proteins ; Phosphotransferases ; Skin ; Skin Neoplasms

There is an error in a grant number in Acknowledgements.

High intensity interval training (HIIT) boosts natural killer (NK) cell number and activity in normal weight breast cancer patients; however, whether this occurs in obese individuals is not well established. The goal of this study was to determine whether HIIT effectively boosts NK cells as a therapeutic strategy against breast cancer in an obese mouse model and in overweight/obese women. Diet induced female C57Bl/6 obese mice were assigned to undergo HIIT for four weeks or remain sedentary. Female participants were subjected to a six weeks HIIT protocol. HIIT mice acclimatized to treadmill running were subsequently injected with 5 × 105 polyoma middle T (MT) breast cancer cells intravenously. NK cell number and activation were monitored using flow cytometry, and tumor burden or lipid content evaluated from histological lung and liver tissues, respectively. In both mice and humans, circulating NK cell number and activation (CD3−NK1.1+CD27+ and CD3−CD56+, respectively) markedly increased immediately after HIIT. HIIT obese mice had reduced lung tumor burden compared to controls following MT challenge, and had diminished hepatic lipid deposition despite minimal body weight loss. Our findings demonstrate that HIIT can benefit obese individuals by enhancing NK cell number and activity, reducing tumor burden, and enhancing metabolic health.
Animals ; Body Weight ; Breast Neoplasms ; Breast* ; Cell Count ; Diet ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural* ; Liver ; Lung ; Mice* ; Mice, Obese ; Obesity ; Running ; Tumor Burden