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Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality and this is associated with poor survival rates. Understanding the molecular genetic changes of gastric carcinoma may offer an insight into its pathogenesis helps in identifying new biomarkers, aid prognostication, and novel treatment targets. Over a past few decades, advances in technology and high throughput analysis have improved understanding of the molecular genetic aspects of gastric cancer. In this article, hierarchy of the changes at genetic and molecular level including several aspects which are heterogenous and represents a wide spectrum such as tumor suppressor genes, oncogenes, cellcycle regulators, apoptosis, cell-adhesion molecules, loss of heterozygosity, microsatellite instability, and epigenetic changes. The classification of gastric carcinoma at molecular and genetic level as well as hereditary gastric carcinoma is elaborated. The molecular genetic aspects regarding pathogenesis, changes and aberrations of all genes and pathways which are involved in gastric cancer are addressed in this review.

MeCP2 (methyl-CpG binding protein 2), an epigenetic regulator, has been shown to regulate the function of neurons and glial cells. Our previous study has demonstrated that MeCP2 repress the myelin gene expression in rat oligodendrocytes but whether MeCP2 bind to myelin gene MBP and PLP is not yet known. Besides oligodendrocytes, C6 glioma also expresses myelin genes and could be used as a model system to study myelin gene expression. In the present study, we determined that MeCP2 directly bind to MBP, PLP, and BDNF promoter in oligodendrocytes. Further, it was found that MeCP2 differentially regulates the myelin gene expression in oligodendrocytes and C6 glioma. In contrast to oligodendrocytes, MeCP2 does not bind to promoter region of MBP and PLP in C6 glioma suggest that MeCP2 differentially regulates the gene expression in different cell types.

Purpose To record the incidence of cognitive dysfunction in edentulous patients suffering from obstructive sleep apnea (OSA) and establish a plausible hypothesis to explain the correlation of cognitive dysfunction and OSA. Materials and methods In this study, 315 edentulous patients (aged 60 to 65 years) visiting the outpatient department at Saraswati Dental College, Lucknow were recruited from January 2013 to October 2015. Prosthodontic Diagnostic Index (PDI) classification was used to assess the intraoral condition to relate it with the span of edentulousness. The BERLIN questionnaire and Epworth Sleepiness Scales were used to diagnose sleep-disordered breathing, following which the patients were put through all-night polysomnography. The apnea-hypopnea index (AHI) scores were derived. Mild and moderate OSA patients were classified into mild, moderate, and severe cognitive dysfunction based on SGRQ-C and SCD. Data were tabulated according to a new classification (Cognitive Dysfunction of Dental Sleep Medicine Patients [CDDSMP] Classification) designed specifically for this study. Data were analyzed using SPSS v15.0. Scores were tabulated as mean ± SD and median [IQR] values. Change from baseline was analyzed using Wilcoxon signed rank test. Results Mean scores at different time intervals were 3.03 ± 1.76 (3 months), 2.98 ± 1.80 (6 months), and 2.81 ± 1.84 (9 months). The median [IQR] values of scores at all time intervals except 9 months were 3 [1 to 5]. At 9 months, median [IQR] was 2 [1 to 5]. A significant change in scores was observed in the 3-month interval (p ≤ 0.001). Conclusions The severity of OSA and neurocognitive dysfunction could be directly related to the PDI classification and the span of edentulousness of the patient and modified mandibular advancement device treatment significantly improved the patients' condition, which was reflective from 3 months post-intervention itself.

avMethyl‑CpG binding protein 2 (MeCP2) is an epigenetic regulator, which preferentially binds to methylated CpG dinucleotides in DNA. MeCP2 mutations have been linked to Rett syndrome, a neurodevelopmental disorder characterized by severe intellectual disability in females. Earlier studies indicated that loss of MeCP2 function in neuronal cells was the sole cause of Rett syndrome. Subsequent studies have linked MeCP2 expression in CNS glial cells to Rett syndrome pathogenesis. In this review, we have discussed the role of MeCP2 in glial subtypes, astrocytes, oligodendrocytes and microglia, and how loss of MeCP2 function in these cells has a profound influence on both glial and neuronal function.

Aberrant PDGFR (Platelet derived growth factor receptor) signalling in brain tumors and gliomas is one of the primary cause of tumor progression. PDGFR stimulation by its ligand and the role of its downstream mediators such as extracellular regulated kinases (ERK1/2), PI3K and ROCK pathways have not been thoroughly investigated. The present study sought to investigate the role of PDGF receptor signalling inhibition on suppression of rat C6 glioma growth and migration. Treatment of C6 cells with PDGFR inhibitor, AG1295 caused a significant reduction in migration and proliferation by regulating the ERK and ROCK signalling. Subsequently, PDGFR blocking was demonstrated to regulate cytoskeleton reorganization by modulating the Actin-pMLC reorganization and pERK–FAK–Paxillin complex formation which may further regulate the C6 glioma migration. Further, other malignant behaviour of C6 glioma such as anchorage independent growth, adhesion, invasion and sphere forming abilities were found to be impaired by PDGFR blocking. PDGFR inhibition further regulates the C6 glioma tumor behaviour by inducing gene expression of GFAP, BDNF, and MECP2 and down regulating FAK expression. In conclusion, our data elucidate novel mechanisms involve in PDGFR inhibition mediated inhibition of C6 glioma growth and migration which can be a future potential target for the treatment of glioma.

Purpose To record the incidence of obstructive sleep apnea (OSA) in nonobese male subjects and investigate the coexistence of lifestyle stress, sleep deprivation, and upper airway inflammation. Materials and methods 552 patients were assessed during a survey of banks, government and corporate offices, recruitment agencies, and schools between January 2012 and January 2016. After applying the inclusion and exclusion criteria designed for this study, the number of patients tapered down to 120 patients who underwent diagnostic tests, viz. polysomnography, chemiluminiscence immunoassay, nephelometry, and upper airway endoscopy. This revealed the presence of OSA coexistent with elevated serum cortisol, C-reactive protein (CRP), and upper airway inflammation. Results Polysomnography showed that 57 of 120 patients suffered from OSA. Objective evaluation of these patients exposed an undercurrent of lifestyle stress in 39 patients. CRP and serum cortisol were found to be significantly high (1.60 ± 0.52 and 7.20 ± 0.76 μg/dL, respectively) in 30 patients. Endoscopy revealed 18 patients with moderate, 7 with severe, and 5 with no upper airway inflammation. Conclusion The results of this study demonstrated that OSA was found to be prevalent in the cohort of nonobese male patients studied. Coexistence of lifestyle stress, sleep deprivation, and upper airway inflammation was revealed.

Purpose To probe in greater detail the changes at the ceramometal interface induced by heat energy absorption, using energy diffraction X-ray spectroscopy (EDS) and scanning electron microscopy (SEM) and correlate these changes with the shear bond strength of porcelain to nickel chromium alloy. Materials and methods Seventy-five strips of nickel-chromium alloy (20 mm long, 5 mm wide, 3 mm thick) were prepared and layered with porcelain, conforming to ANSI/ADA specification no. 38 (for Metal-Ceramic Dental Restorative Systems: 2010). These test specimens were divided equally into three groups. Specimens of each group (25) were fired to a specific temperature range, that is 700°C, 900°C, and 960°C. SEM and EDS were performed on all specimens, at the metal alloy/ceramic interface. Bonding of the ceramic layer to the metal alloy was evaluated by a shear bond strength test as per ANSI/ADA specification no. 38. The data were recorded and analyzed using one-way ANOVA and post hoc Tukey HSD test. Results SEM images of the porcelain/metal alloy interface revealed roughness of the metal alloy surface adjacent to the ceramic layer. EDS study revealed that an oxygen depletion zone was formed at the interface region, facilitating the formation of intermetallic compounds. The mean shear bond strength showed an upward trend until 900°C and decreased thereafter. Conclusion Formation of intermetallic compounds at the interface, in the presence of an oxygen depletion zone, was the prime factor in bonding of porcelain to metal alloy. This provides a new concept of ceramometal bonding.

Purpose To estimate the incidence of obstructive sleep apnea (OSA) in elderly edentulous patients (aged 60-65 years) and investigate a correlation of serum serotonin levels with the apnea-hypopnea index (AHI), respiratory effort-related arousal (RERA), and respiratory disturbance index (RDI). Materials and methods 381 elderly completely edentulous patients (307 male, 74 female) aged 60 to 65 years with a history of edentulism of 12 to 15 months, seeking oral rehabilitation at the prosthodontic clinic at Saraswati Dental College & Hospital, Lucknow, India, between January 2014 and January 2016 were enrolled for the present study. After application of the inclusion and exclusion criteria of this study, 183 patients (162 male, 21 female) who were found susceptible, were subjected to the BERLIN questionnaire and Epworth Sleepiness Scale (ESS) to assess sleep disordered breathing (SDB) and then put through all-night polysomnography (PSG). On the basis of AHI, RERA, and RDI scores, 156 patients (143 male, 13 female) who tested positive for OSA were classified according to its intensity. All 156 patients underwent body-mass index (BMI) estimation, cephalometry, and intraoral examination for skeletal and soft tissue profile record. Serum serotonin was estimated from whole blood samples for the 156 OSA and the 27 normal patients. The 156 (147 nonobese, 9 obese) OSA-positive patients were provided with complete dentures and were trained to use the same as a modified mandibular advancement device (MAD) during sleep at night. These patients were kept on a quarterly follow-up for 9 months. Data collected was subjected to statistical analysis, and inferences drawn. Results The incidence of OSA in elderly edentulous subjects was found to be 32.03% in males and 8.91% in females. A mere 9 out of 156 (5.76%) elderly edentulous OSA patients were found to be obese (Class I) on the basis of BMI estimation. Cephalometry of the patients showed that they had a skeletal class I maxillomandibular relationship. AHI scores of nonobese patients revealed that most of the patients had moderate OSA, followed by mild OSA and severe OSA. Serum serotonin levels ranged from 53 to 83 ng/dL. AHI score of the 9 obese patients were in the moderate to severe range, and their serum serotonin levels were 60 to 70 ng/dL. A correlation between severity of OSA and serum serotonin level was validated in this study. Conclusion OSA was found to be prevalent in edentulous subjects due to pharyngeal collapse and decreased neuromuscular control. An inverse relationship of serum serotonin levels and AHI scores was established.

Gastric cancer (GC) is a serious fatal cancer on a global scale because of its presentation at advanced stage. The expressions of vascular endothelial growth factor (VEGF), E-cadherin, and matrix metalloproteinases (MMPs) in other cancers have been reported. However, its expression and underlying mechanisms are little known in gastric cancer in Indian context. In this study, we detected mRNA expression of VEGF, E-cadherin, and MMPs (MMP-1, MMP-2, and MMP-9) in 73 gastric cancer tissues and 27 normal controls by reverse-transcriptase polymerase chain reaction (RT-PCR). Receiver operator characteristics analysis was done for determining the diagnostic utility of VEGF, MMPs and E-cadherin with respect to the sensitivity and specificity. The association of VEGF, MMPs, and E-cadherin expression with the clinicopathological characteristics and the prognosis was subsequently analyzed. The mRNA expression results showed that E-cadherin was significantly downregulated in 47.9% of GC in comparison to control. There was no change in VEGF expression observed in 90.4% GC cases. MMP-1, MMP-2, and MMP-9 were overexpressed in 13.7%, 28.8%, and 11% of GC, respectively, with significant change in MMP-2 (p ≤ 0.0001) and MMP-9 (p = 0.027) in comparison to control. Our results strengthen the necessity of more studies to elucidate the prophetic role of these genes in the development of gastric cancer.

Oligodendrocyte progenitor cells (OPCs) originate from the sub-ventricular zone of the developing brain. They migrate and proliferate to occupy the white matter tracts of the central nervous system and transform into myelinating oligodendrocytes. Along their route of migration, OPCs are guided and controlled by several growth factors and chemokines. PDGF-A (platelet-derived growth factor), a growth factor, serves as a monogenic and mitogenic cue during the process and activates intracellular signaling pathways inside the cell. Activation of extracellular signal regulated kinase (ERK) signaling is one of the mechanisms by which PDGF-A induces the migration of OPCs. However, the mechanisms governing the PDGF-A-induced ERK-driven OPCs migration are still unclear. In the current study, we investigated further the role of PDGF-A-induced ERK signaling in OPC migration. First, we confirmed the role of PDGF-A-activated ERK signaling in OPC migration using the pharmacological inhibitor U0126, or siRNA-mediated suppression of ERK expression. Then, we demonstrated that PDGF-A-induced actin reorganization and interaction of focal adhesion kinase (FAK), Paxillin, and pERK signals are impaired in OPCs treated with the MEK inhibitor U0126. Thus, our findings demonstrated that PDGF-A induces OPC migration in an ERK-dependent mechanism via regulation of actin reorganization and FAK-Paxillin interaction.

Purpose To study the structural changes occurring in the dental porcelain mass fired at various firing temperatures using scanning electron microscopy (SEM) and X-ray diffraction (XRD) spectroscopy. Also, additional tests, namely compressive strength, abrasion resistance analysis, and the amount of oxides released, were conducted at different firing temperatures. Materials and Methods Six groups (40 specimens in each group) of porcelain mass were prepared. The dimensions and weight of all the specimens were kept constant. The specimens were then heat treated at different firing temperatures (660°C, 760°C, 860°C, 900°C, 960°C, 990°C). Half of the specimens of each group were subjected to a compressive strength test on a universal testing machine and then finely ground using an electrochemical grinder to prepare for XRD analysis. The other half of the specimens was weighed to analyze the amount of oxides released after each firing cycle. Following this, the specimens underwent an abrasion resistance test on a Nanovea Tribometer. The unaltered surface was scanned using SEM. The data (numerical and graphical) for all the tests were recorded and analyzed using one-way ANOVA and post hoc Tukey test. Results The specimens fired at 900°C exhibited superior compressive strength and abrasion resistance. The quantity of oxides released by the specimens fired at 900°C was the least compared to specimens heat treated at the other firing temperatures. XRD analysis proved that the oxide released by the porcelain mass was calcium aluminum chromium oxide. Also, the fewer peaks obtained in the XRD graphs of specimens fired at 900°C signified lesser porosities in the porcelain specimens. SEM analysis depicted a homogeneous mass of porcelain at 900°C. Conclusion All the above findings validate the objective of studying the physical and internal structural changes of dental porcelain when subjected to an increasing firing temperature gradient. The specimens fired at 900°C exhibited superior strength and abrasion resistance. SEM analysis depicted a homogeneous mass of dental porcelain, implying that firing was complete at 900°C.

Quercetin (Qu), is a flavonoid known to have anti-diabetic effects owing to its antioxidant property, thus promoting regeneration of the pancreatic islets, ultimately increasing insulin secretion. But the therapeutic application of Qu is hampered by its low oral bioavailability and its unfavourable physicochemical characteristics. The present work aimed at formulation of Quercetin loaded Soluplus® micelles (SMs) so as to enhance its bioavailability and provide prolonged release for the management of diabetes. Box-Behnken response surface methodology was employed to optimize the formulation prepared using co-solvent evaporation method. Physicochemical characterization confirmed the nano-spherical nature of Quercetin loaded Soluplus® micelles (Qu-SMs) with average particle size ranging from 85-108nm, encapsulation efficiency of 63-77%. Solid state characterization confirmed the encapsulation of Qu in the micelles without any incompatibilities. Moving forward, the results of in vitro study revealed prolonged and slow release of Qu from the developed formulations. The in vivo pharmacokinetic study revealed improved bioavailability by enveloping the drug in SMs. Moreover, the study performed to evaluate the efficiency in diabetes treatment revealed an enhanced anti-diabetic effect. Thus, Qu-SMs can serve as potential carriers aimed at improving the anti-diabetic property of Qu.