Extendable high gain low current/high pulse modified quadratic-SEPIC converter for water treatment applications.

Substantial attention has been drawn over the past few years by high step-up dc-dc converters owing to their applications in a wide range. Apart from renewable energy applications, high voltage/ high pulse converters are efficiently used in water treatment applications. The converter suggested a combination of Quadratic and SEPIC converters with a diode-capacitor cell. This topology generates high-voltage repetitive pulses with a single semiconductor switch and reduced component count. The stress across the components is less than the high-gain converters reported in the literature. The topology has an extendable feature by increasing the number of diode-capacitor cells without affecting the stress. The superiority of the high pulse generating topology is validated with a similar converter in the literature. This paper discusses the nL5 simulator results for the proposed rated topology required for water treatment. A scaled-down 50 W prototype is tested for various input voltages to generate high voltage pulse, and the analytical study is validated.

Biocomposite-based strategies for dental bone regeneration.

OBJECTIVE: Because of the anatomical complexity of the oral and maxillofacial sites, repairing bone defects in these regions is very difficult. This review article aims to consider the application of biocomposites-based strategies for dental bone regeneration. STUDY DESIGN: Research papers related to the topic, published over the last 20 years, were selected using the Web of Science, Pubmed, Scopus, and Google Scholar databases. RESULTS: The strategies of monophasic, biphasic/multiphasic scaffolds, and biopolymer-based nanocomposite scaffolds containing nanomaterials compared with traditional methods used for bone regeneration, such as autografts, allografts, xenografts, and alloplasts are found to be superior because of their ability to overcome the issues (e.g., limited bone sources, pain, immune responses, high cost) related to the applications of the traditional methods. CONCLUSIONS: In addition, additive manufacturing technologies were found to be highly advantageous for improving the efficacy of biocomposite scaffolds for treating dental bone defects.

Prevalence and morphological analysis of isthmuses in mandibular molars of the Indian population: A micro-computed tomographic study.

Objectives: This study evaluated the prevalence, configurations, and correlation of isthmuses at coronal, middle, and apical root 3rd in mandibular molars of the Indian population using micro-computed tomography µCT). Materials and Methods: One hundred and five permanent mandibular molar teeth were scanned under µCT. The axial sections were analyzed at the coronal, middle, and apical thirds of the root for isthmus types and classified according to Hsu and Kim's classification. Descriptive statistics for each isthmus type were calculated. The correlations between the apical, middle, and coronal thirds of the root were determined using Pearson's correlation coefficient. Results: Type IV isthmus was the most common in the coronal third of the mesial root of mandibular 1st molar (42.9%), while Type V was prevalent in the coronal third of the mesial root of 2nd molar (42.9%). Type I isthmus was found to be highly prevalent in the middle 3rd (71.4%) and apical 3rd (61.9%) of mesial roots of 1st molars, and in the middle 3rd (71.4%) and apical 3rd (42.9%) of mesial roots of 2nd molars. Type V isthmus was the most prevalent in all the thirds of the distal roots of both 1st and 2nd molars, ranging from 40% to 50%. Furthermore, a strong correlation of 0.965 (P < 0.01) was found between the isthmuses in the apical and middle thirds of roots. Conclusion: There are variations in the prevalence and type of isthmuses across different sections of the root, including the presence of atypical isthmuses. Micro-CT with high-resolution imaging and three-dimensional reconstruction is crucial for investigating root canal morphology. Clinicians could benefit from considering demographic characteristics to better predict the presence of isthmus variations. Clinical Relevance: The isthmus configurations and frequency differ at each section of mandibular teeth.

Advanced Drug Delivery Platforms for the Treatment of Oral Pathogens.

The oral cavity is a complex ecosystem accommodating various microorganisms (e.g., bacteria and fungi). Various factors, such as diet change and poor oral hygiene, can change the composition of oral microbiota, resulting in the dysbiosis of the oral micro-environment and the emergence of pathogenic microorganisms, and consequently, oral infectious diseases. Systemic administration is frequently used for drug delivery in the treatment of diseases and is associated with the problems, such as drug resistance and dysbiosis. To overcome these challenges, oral drug delivery systems (DDS) have received considerable attention. In this literature review, the related articles are identified, and their findings, in terms of current therapeutic challenges and the applications of DDSs, especially nanoscopic DDSs, for the treatment of oral infectious diseases are highlighted. DDSs are also discussed in terms of structures and therapeutic agents (e.g., antibiotics, antifungals, antiviral, and ions) that they deliver. In addition, strategies (e.g., theranostics, hydrogel, microparticle, strips/fibers, and pH-sensitive nanoparticles), which can improve the treatment outcome of these diseases, are highlighted.

Natural stain (Kumkum) formulated by the extract of Curcuma aromatica and slaked lime in histostaining of oral tissues: An observational study.

BACKGROUND: The pharmacological actions of Curcuma aromatica (wild turmeric) such as anti-inflammatory, antitumor, antifungal, antimicrobial and wound healing have been recognized since ages. However, its role as a natural histological stain has not been explored till date. AIM: To evaluate the efficacy of natural substance-Kumkum prepared from the extract of C. aromatica and slaked lime in staining the biopsied oral tissues. MATERIALS AND METHODS: A cohort study that used 60 formalin fixed paraffin embedded soft and hard tissue specimens from institutional archives were subjected to sectioning and stained using Kumkum and hematoxylin and eosin (H and E). The slides were evaluated for their staining efficacy and results were statistically analyzed using Wilcoxon signed-rank test and Independent 't' test. RESULTS: The mean of the overall parameters assessed for staining efficacy did not show statistically significant difference between the study groups in normal and pathological specimens for tooth (P = 0.410 and 0.484), bone (P = 0.133 and 0.157) and soft tissues (P = 0.186 and 0.113), respectively. This suggests that Kumkum staining efficacy is equivalent to that of routine H and E for oral tissues. Structures such as dentinoenamel junction, dentinal tubules, incremental lines of cementum, reversal and resting lines, osteocytic canaliculi, mature and immature bone could be appreciated better in Kumkum stained slides, thereby rendering a special staining property to Kumkum stain. CONCLUSION: To our knowledge, this study is the first of its kind to have used Kumkum stain obtained from C. aromatica for the differentiation of the components of tooth, bone and soft tissue structures in histostaining of oral tissues. The naturally prepared Kumkum stain possesses dual staining property both in routine and differential staining. This facilitates diagnosis of fibro-osseous lesions, bony, collagen and muscular pathologies. The natural stain also finds application in forensic odontology for age estimation.

PECAM-1 overexpression signifies aggressive biologic behavior of oral lichen planus - A pilot study.

CONTEXT: The etiopathogenesis of oral lichen planus (OLP) is still debatable. According to literature, many studies have illustrated OLP as a T-cell-mediated chronic autoimmune disease. Currently, there is increased evidence of chronic inflammation in OLP and its association with vascular adhesion molecules (VAMs). AIM: The aim of this study was to evaluate the expression of VAM (PECAM-1) in OLP. SETTING AND DESIGN: Tissue samples involved 20 archival cases of histopathologically confirmed OLP (n = 15) and normal mucosa (n = 5) as controls. MATERIALS AND METHODS: The sections were subjected to immunohistochemical analysis using antibody to PECAM-1. Brown staining of the endothelial cells of blood vessels was considered positive. The expression of PECAM-1 in OLP was statistically analyzed using Wilcoxon sign-rank test. RESULTS: The expression of PECAM-1 in OLP was statistically significant when compared with normal mucosa (P < 0.05). A statistically significant difference was also observed in PECAM-1 expression between the reticular type and erosive type of OLP. CONCLUSION: PECAM-1 was found to be overexpressed in OLP; difference in PECAM-1 expression was noted between the reticular and erosive types. The VAMs could be exploited as a possible therapeutic target in OLP to modulate the disease process thereby reducing the dependency on corticosteroids.

Lactation induces increases in the RANK/RANKL/OPG system in maxillary bone.

The underlying causes of maxillary bone loss during lactation remain poorly understood. We evaluated the impact of lactation on physiological and mechanically-induced alveolar bone remodeling. Nulliparous non-lactating (N-LAC) and 21-day lactating (LAC) mice underwent mechanically-induced bone remodeling by orthodontic tooth movement (OTM). Micro-computed tomography (microCT) was performed in the maxilla, femur and vertebra. Tartrate-resistant-acid phosphatase (TRAP) and Masson's trichrome labelling was performed in the maxillary bone and gene expression was determined in the periodontal ligament. The effect of prolactin on osteoclast (OCL) and osteoblast (OBL) differentiation was also investigated in N-LAC and LAC mice. Lactation increased alveolar bone loss in the maxilla, femur and vertebra, while OTM was enhanced. The number of OCL and OBL was higher in the maxilla of LAC mice. OTM increased OCL in both groups; while OBL was increased only in N-LAC but not in LAC mice, in which cell numbers were already elevated. The alveolar bone loss during lactation was associated with increased expression of receptor activator of nuclear factor-KappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in the maxilla. OTM induced the same responses in N-LAC mice, whereas it had no further effect in LAC mice. Lactation enhanced differentiation of OCL and OBL from bone marrow cells, and prolactin recapitulated OCL differentiation in N-LAC mice. Thus, lactation increases physiological maxillary bone remodeling and OTM, and both require activation of RANK/RANKL/OPG system. These findings expand our knowledge of lactation-induced osteopenia and have possible impact on clinical practice regarding orthodontic treatments and dental implants in lactating women.

Scriptaid cause histone deacetylase inhibition and cell cycle arrest in HeLa cancer cells: A study on structural and functional aspects.

Scriptaid (SCR), a well-known histone deacetylase inhibitor, cause various cellular effects such as cell growth inhibition and apoptosis. In this study, we have evaluated the anti-cancer effects of Scriptaid in HeLa cells, IMR-32 and HepG2 cells. Scriptaid inhibited the growth of HeLa cells with IC50 of 2µM at 48h in a dose-dependent manner. Flow-cytometric analysis indicated that SCR induced apoptosis. Scriptaid was found to inhibit HDAC-8 effectively than other HDAC inhibitor such as TSA as observed by HDAC-8 assay, Western blotting and modelling study. This observation was further strengthened by an artificial neuronal network (ANN) model.

Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster.

Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR-13 and miR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species (ROS) level to trigger apoptotic cell death.

Histomorphometric and histologic evaluation of titanium-zirconium (aTiZr) implants with anodized surfaces.

The choice of implant surface has a significant influence on osseointegration. Modification of TiZr surface by anodization is reported to have the potential to modulate the osteoblast cell behaviour favouring more rapid bone formation. The aim of this study is to investigate the effect of anodizing the surface of TiZr discs with respect to osseointegration after four weeks implantation in sheep femurs. Titanium (Ti) and TiZr discs were anodized in an electrolyte containing DL-α-glycerophosphate and calcium acetate at 300 V. The surface characteristics were analyzed by scanning electron microscopy, electron dispersive spectroscopy, atomic force microscopy and goniometry. Forty implant discs with thickness of 1.5 and 10 mm diameter (10 of each-titanium, titanium-zirconium, anodized titanium and anodized titanium-zirconium) were placed in the femoral condyles of 10 sheep. Histomorphometric and histologic analysis were performed 4 weeks after implantation. The anodized implants displayed hydrophilic, porous, nano-to-micrometer scale roughened surfaces. Energy dispersive spectroscopy analysis revealed calcium and phosphorous incorporation into the surface of both titanium and titanium-zirconium after anodization. Histologically there was new bone apposition on all implanted discs, slightly more pronounced on anodised discs. The percentage bone-to-implant contact measurements of anodized implants were higher than machined/unmodified implants but there was no significant difference between the two groups with anodized surfaces (P > 0.05, n = 10). The present histomorphometric and histological findings confirm that surface modification of titanium-zirconium by anodization is similar to anodised titanium enhances early osseointegration compared to machined implant surfaces.

Novel Etoposide Analogue Modulates Expression of Angiogenesis Associated microRNAs and Regulates Cell Proliferation by Targeting STAT3 in Breast Cancer.

Tumor microenvironment play role in angiogenesis and carcinogenesis. Etoposide, a known topoisomerase II inhibitor induces DNA damage resulting in cell cycle arrest. We developed a novel Etoposide analogue, Quinazolino-4ß-amidopodophyllotoxin (C-10) that show better efficacy in regulating cell proliferation and angiogenesis. We evaluated its role on expression of microRNAs-15, 16, 17 and 221 and its targets Bcl-2, STAT3 and VEGF that dictate cell proliferation and angiogenesis. Docking studies clearly demonstrated the binding of Etoposide and C-10 to STAT3. We conclude that combination of Etoposide or C-10 with miR-15, 16, 17 and 221 as a new approach to induce apoptosis and control angiogenesis in breast cancer.

Spark anodization of titanium-zirconium alloy: surface characterization and bioactivity assessment.

Titanium (Ti) and its alloys have been popularly used as implant biomaterial for decades. Recently, titanium-zirconium (TiZr) alloy has been developed as an alternative implant material with improved strength in load bearing areas. Surface modification is one of the key factors to alter the surface properties to hasten osseointegration. Spark anodic oxidation (anodization) is one such method that is reported to enhance the bone formation around implants. This study aims to anodize TiZr and study its surface characteristics and cytocompatibility by cell culture experiments using osteoblast-like cells. Titanium (Ti) and TiZr discs were anodized in an electrolyte containing DL-α-glycerophosphate and calcium acetate (CA) at 300 V. The surface characteristics were analyzed by scanning electron microscopy, electron dispersive spectroscopy, X-ray diffraction (XRD), atomic force microscopy and goniometry. Using osteoblast-like cells viability, proliferation, differentiation and mineralization was assessed. The anodized surfaces demonstrated increased oxygen, entrapped calcium and phosphorous from the electrolyte used. XRD analysis confirmed the presence of anatase in the oxide layer. Average roughness increased and there was a significant decrease in contact angle (P < 0.01) following anodization. The anodized TiZr (aTiZr) surfaces were more nano-porous compared to anodized Ti (aTi). No significant difference was found in the viability of cells, but after 24 h the total number of cells was significantly higher (P < 0.01). Proliferation, alkaline phosphatase activity and calcium deposits were significantly higher on anodized surfaces compared to machined surfaces (P < 0.05, ANOVA). Anodization of TiZr resulted in a more nanoporous and hydrophilic surface than aTi, and osteoblast biocompatibility appeared comparable to aTi.

MiR-15/16 complex targets p70S6 kinase 1 and controls cell proliferation in MDA-MB-231 breast cancer cells.

BACKGROUND: MicroRNAs are small non-coding RNAs that regulate post-transcriptional mRNA expression by binding to 3' untranslated region (3'-UTR) of the complementary mRNA sequence resulting in translational repression and gene silencing. They act as negative regulators of gene expression and play a pivotal role in regulating apoptosis and cell proliferation. Studies have shown that miRNAs interact with p53 by regulating the activity and function of p53 through direct repression or its regulators. Mammalian target of rapamycin (mTOR) is an evolutionary conserved check point protein kinase that plays a major effect in the control of cell division via protein synthesis regulation. mTOR regulates protein synthesis through phosphorylation and inactivation of 4E-BP1 and through phosphorylation and activation of S6 kinase 1 (S6K1). These two downstream effectors of mTOR control cell growth and metabolism. In mammals, mTOR protein kinase is the central node in the nutrient and growth factor signaling and p53 plays a critical role in sensing genotoxic stress. Activation of p53 inhibits mTOR activity, which in turn regulates its downstream targets providing a cross talk among both the signaling machinery. MicroRNA-15 and 16 belong to a common precursor family and are highly conserved. Deletion or downregulation of these two microRNAs has been shown to accelerate cell division by modulating the expression of the genes involved in controlling cell cycle progression. These microRNAs may function as tumor suppressors and act on the downstream targets of p53 signaling pathway. To have a better insight of the role of miR-15/16 in regulating the cross talk of p53 and mTOR, we performed an in depth study in MDA-MB-231 breast cancer cells by performing a gain-of-function analysis with lentiviral plasmids expressing microRNA-15 and 16. METHODS: The effect of individual microRNAs on RPS6KB1 was examined by using 3'-UTR clones via luciferase based assays. The cell cycle effects were observed by flow-cytometric analysis. Reverse transcription PCR was used to explore the expression of mTOR and RPS6KB1 in cells transfected with miR-15/16. RESULTS: Overexpression of miR-15/16 led to inhibition of cell proliferation causing G1 cell cycle arrest as well as caspase-3 dependent apoptosis. Forced expression of miR-15/16 might lead to decrease in mRNA level of RPS6KB1, mTOR. The effect was a complete reversal after treatment with anti-miRs against miR-15/16 proving the specificity of the expression. In addition, the dual luciferase reporter assays indicated a clear decrease in luciferase gene expression in cells transfected with lentiviral based miR-15 and 16 plasmids indicating that miR-15/16 directly targets RPS6KB1 through its 3'-UTR binding. Further, these microRNAs also inhibit epithelial to mesenchymal transition (EMT) by targeting key proteins such as Twist1 and EZH2 clearly demonstrating its crucial role in controlling cell proliferation. CONCLUSION: This study suggests that exogenous microRNA-15/16 can target RPS6KB1, control cell proliferation and cause apoptosis in caspase-dependent manner even in the absence of functional p53.

Novel anthranilamide-pyrazolo[1,5-a]pyrimidine conjugates modulate the expression of p53-MYCN associated micro RNAs in neuroblastoma cells and cause cell cycle arrest and apoptosis.

It has previously been shown that anthranilamide-pyrazolo[1,5-a]pyrimidine conjugates activate p53 and cause apoptosis in cervical cancer cells such as HeLa and SiHa. Here we establish the role of these conjugates in activating p53 pathway by phosphorylation at Ser15, 20 and 46 residues and downregulate key oncogenic proteins such as MYCN and Mdm2 in IMR-32 neuroblastoma cells. Compounds decreased the proliferation rate of neuroblastoma cells such as IMR-32, Neuro-2a, SK-N-SH. Compound treatment resulted in G2/M cell cycle arrest. The expression of p53 dependent genes such as p21, Bax, caspases was increased with concomitant decrease of the survival proteins as well as anti-apoptotic proteins such as Akt1, E2F1 and Bcl2. In addition the expression of important microRNAs such as miR-34a, c, miR-200b, miR-107, miR-542-5p and miR-605 were significantly increased that eventually lead to the activation of apoptotic pathway. Our data revealed that conjugates of this nature cause cell cycle arrest and apoptosis in IMR-32 cells [MYCN (+) with intact wild-type p53] by activating p53 signalling and provides a lead for the development of anti-cancer therapeutics.

Synthesis and biological evaluation of diaryl ether linked DC-81 conjugates as potential antitumor agents.

A series of new diaryl ether linked pyrrolobenzodiazepine (PBD) conjugates (4a-i, 5a-i and 6a-f) was synthesized and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. These conjugates exhibited significant anticancer activity with GI50 values in the range of 0.1-3.88 µM. Some of the potent conjugates (4b, 4h, 5h, 6b, 6c and 6e) were further investigated on cell cycle distribution. FACS analysis showed the accumulation of cells in G0 phase indicating the apoptosis inducing nature of these conjugates. Moreover, compound 6b caused a decrease in the mitochondrial membrane potential, which indicates the apoptotic nature of the compound through mitochondrial mediated pathway. Further conjugates 4b, 4h and 6b induce the activation of caspase and PARP proteins, followed by apoptotic cell death in MCF7 cell line.

Imidazo-benzothiazoles a potent microRNA modulator involved in cell proliferation.

MicroRNAs are endogenously expressed tiny non-coding RNAs that control gene expression at the post-transcriptional level and regulate processes of cell growth, differentiation, proliferation and apoptosis. Aberrant expression of microRNAs correlates with various cancers. Our experiments demonstrated that imidazo-benzothiazole conjugates caused apoptosis in colon cancer cells by modulating the expression of microRNAs. In vivo study in Drosophila melanogaster has exhibited inhibitory action on bantam microRNA, the homolog of human miR-542-5p that is involved in deciding the cellular cues that regulate the balance between proliferation and apoptosis. The expression of direct targets of bantam such as Hid and HDAC-6 were affected upon compound treatment. Interestingly, these conjugates downregulate the genes involved in microRNA biogenesis such as Drosha, Pasha and Dicer-1. Our findings have elucidated the microRNA inhibitory role of imidazo-benzothiazole conjugates.

Decolourization of textile dye effluent by non-viable biomass of Aspergillus fumigatus

The aim of this work was to study the decolourization of textile dye effluent by non-viable biomass of Aspergillus fumigates. The dried non-viable fungal biomass exhibited maximum dye removal at pH 7.0 with temperature of 30ºC and 3 g/l (w/v) biomass concentration, after 24 h contact time. The results showed that the non-viable biomass possessed high efficiency for dye removal from textile effluent.

Synthesis and biological evaluation of 4ß-sulphonamido and 4ß-[(4'-sulphonamido)benzamide]podophyllotoxins as DNA topoisomerase-IIα and apoptosis inducing agents.

A series of new 4ß-sulphonamido and 4ß-[(4'-sulphonamido)benzamide] conjugates of podophyllotoxin (11a-j and 15a-g) were synthesized and evaluated for anticancer activity against six human cancer cell lines and found to be more potent than etoposide. Some of the compounds 11b, 11d and 11e that showed significant antiproliferative activity in Colo-205 cells, were superior to etoposide. The flow cytometric analysis indicates that these compounds (11b, 11d and 11e) showed G2/M cell cycle arrest and among them 11e is the most effective. It is observed that this compound (11e) caused both single-strand DNA breaks as observed by comet assay as well as double-strand DNA breaks as indicated by γ-H2AX. Further 11e showed inhibition of topo-IIα as observed from Western blot analysis and related studies. Compounds caused activation of ATM as well as Chk1 protein indicating that the compound caused effective DNA damage. Moreover activation of caspase-3, p21, p16, NF-kB and down regulation of Bcl-2 protein suggests that this compound (11e) has apoptotic cell death inducing ability, apart from acting as a topo-IIα inhibitor.

Synthesis, anticancer activity and apoptosis inducing ability of bisindole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

A series of bisindole-pyrrolobenzodiazepine conjugates (5a-f) linked through different alkane spacers was prepared and evaluated for their anticancer activity. All compounds exhibited significant anticancer potency and the most potent compounds 5b and 5e were taken up for detailed studies on MCF-7 cell line. Cell cycle effects were examined apart from investigating the inhibition of tubulin polymerization for compounds 2a, 2b, 5b and 5e at 2µM. FACS analysis showed that at higher concentrations (4 and 8µM) there was an increase of sub-G1 phase cells and decrease of G2/M phase cells, thus indicating that compounds 5b and 5e are effective in causing apoptosis in MCF-7 cells. It was also observed that compounds 5b and 5e showed the down regulation of histone deacetylase protein levels such as HDAC1, 2, 3, 8 and increase in the levels of p21, followed by apoptotic cell death. The apoptotic nature of these compounds was further evidenced by increased expression of cleaved-PARP and active caspase-7 in MCF-7 cells.